Introdução: Mundialmente, o câncer de mama é o tipo com maior incidência e mortalidade na população feminina. Tanto os tumores primários quanto os metastáticos são tratados com drogas quimioterápicas, muitas vezes pouco seletivas, que atacam o câncer e as células normais.Para melhorar a adesão e reduzir os efeitos adversos, pesquisas vêm desenvolvendo metodologias baseadas em produtos naturais como as isobutilamidas graxas, tornando-se uma excelente alternativa, uma vez que estudos anteriores já relacionaram a atividade anticancerígena de oleamidas e anandamidas (amidas graxas), além disso nanosistemas entregadores de fármacos conseguem aumentar a biodisponibilidade e a concentração dos princípios ativos nos tumores mamários. Objetivo: Realizar semi-síntese de isobutilamidas de ácidos graxas a partir do óleo da andiroba, encapsular isobutilamidas em um sistema de distribuição de fármacos nanoestruturado contendo fibroína da seda, avaliar a estabilidade físico-química, coloidal e por última aplicar o sistema CLN/FAA-FS em linhagem de células de adenocarcinoma de mama murina 4T1 para avaliar o potencial citotóxico. Métodos: Para a obtenção das isobutilamidas, foi realizada uma reação de amidação direta a partir do óleo de andiroba e, em seguida, as isobutilamidas graxas foram caracterizadas por técnicas espectroscópicas (CG-MS, FT-IR e RMN 13H). As isobutilamidas graxas foram incorporadas no carreador lipídico nanoestruturado, contendo a fibroína da seda, como fase surfactante. Para determinar o tamanho da gotícula, perfil do índice de polidispersão (PdI) e potencial zeta (PZ) do nanocarreador nanoestruturado foi realizado o ensaio da estabilidade físico-química e coloidal em diferentes meios biológicos e a viabilidade celular contra linhagens celulares 4T1 e fibroblastos foi determinada através de ensaio de citotoxicidade. Resultados e discussão: Os resultados obtidos na semi-síntese mostraram que a N-isobutiloleamida foi o principal produto da reação (44%), sendo posteriormente confirmado na espectrometria de massa (MS) por impacto de elétrons (70 eV) com íon molecular de 337 m/z e pico base de 115 m/z. A avaliação físico-química da formulação mostrou baixos valores de índice de polidispersão (≤ 0,3) e tamanho médio de partícula ideal. Os resultados encontrados para NLC-FAA/SF em relação ao tamanho médio das partículas foi de 143,9 nm, PZ foi de -8,33 mV e PdI foi de 0,223, mostrando distribuição monodispersa, por último o ensaio colorimétrico Sulforodamina B detectou uma redução na viabilidade celular para culturas de células 4T1 incubadas com 0,18 ± 0,06 μg/mL de sistema nanoestruturado contendo isobutilamidas e fibroína de seda (CLN-FAA/FS). Conclusões: O óleo da andiroba é utilizado pelos povos originários para as mais diversas enfermidades, incluindo o câncer, o óleo é rico em triglicerídeos e ácidos graxos e essa característica torna o óleo uma excelente fonte lipídica para a síntese de FAA, o CLN mostrou-se um eficiente carreador lipídico para aprisionar as isobutilamidas, isto foi confirmado através do ensaio físico-químico e coloidal, além disso o sistema CLN/FAA-FS apresentou elevada citotoxicidade frente as células 4T1 e nenhuma citotocidade para fibroblastos saudáveis, isso é importante porque mostrou seletivo para as células tumorais e seguro para células saudáveis, diante destes achado, o sistema CLN/FAA-FS tem potencial para tornar-se um medicamente, contudo estudo futuros ainda precisam ser realizados, afim de que se possa conhecer sua farmacocinética e farmacodinâmica.

Introduction: Systemic arterial hypertension (SAH) is one of the most prevalent chronic
diseases worldwide, and causes several other complications, having also been identified
among the risk factors for COVID-19. Objective: The present study aimed to determine the
impact of COVID-19 on the metabolomic profile and correlate it with the plasmatic levels of
losartan (LOS) and its active metabolite (EXP3174), biochemical markers and blood
pressure (BP) control in hypertensive patients. Methodology: Patients were divided in four
groups, named: hypertensive with (HCP) and without (HCN) prior diagnosis of COVID-19,
normotensive with (NCP) and without (NCN) prior diagnosis of COVID-19. Their
metabolomic profiles were identified by 1H NMR and plasmatic levels of LOS and EXP3174,
by liquid chromatography coupled to mass-mass spectroscopy, which were correlated with
each other, with blood pressure control and biochemical markers related to COVID-19.
Results and discussion: About 40.5% of patients reached the minimum therapeutic levels
of EXP3174: 40% in the HCP group and 35.3% in the HCN group. The remaining patients
did not reach therapeutic levels of LOS or EXP3174 before, 1.5h or 3h after oral
administration of LOS. For these patients, the dose of LOS should be adjusted in order to
obtain the therapeutic effect. Even though part of the patients reached the therapeutic levels
of EXP3174, a considerable number maintained high BP levels: 10% in the HCP group and
17.6% in the HCN group. This is an important finding, considering that uncontrolled SAH is
a predisposing factor for several complications, such as heart failure and chronic kidney
disease. Therefore, it is prudent that these patients have their therapeutic scheme revised,
so that the clinical outcome of the antihypertensive treatment is achieved. No significant
difference regarding the pharmacokinetics and pharmacodynamics of LOS and EXP3174
was attributed to COVID-19, although BP control was affected, even in patients of the NCP
group, where 28% had BP levels above normal.Regarding the biochemical analysis, the
levels of CRP and glucose were found augmented in the HCP group. CRP may be related

to several conditions, for instance, it is found increased after a positive diagnosis for COVID-
19, the glucose levels also found elevated in the metabolomic results, may indicate that both

hypertension and COVID-19 are factors that contribute to the dysregulation of its plasmatic
levels. According to the metabolomic results, it was possible to identify several biomarkers
related to SAH or COVID-19, such as: alanine, glutamine, arginine, glucose, erythritol,
homogentisate, o-tyrosine, creatinine, 2-hydroxybutyrate and choline. Conclusion: An
expressive number of hypertensive patients did not reach therapeutic levels of LOS and
EXP3174, while BP control was also limited, also detected in some normotensive patients.
Metabolomics proved to be an important tool to assess the effectiveness of the
pharmacotherapy and also the damage caused by SAH and COVID-19 in hypertensive
patients.

Introduction: Hypercholesterolemia can lead to serious cardiovascular damage and is
a condition affecting at least 10 million individuals worldwide. In Brazil, this number can
range from 250,000 to 300,000, with most cases being associated with genetic
polymorphisms in the context of dietary factors and other lifestyle-related factors. For
its treatment, medications from the statin class are used, primarily simvastatin,
atorvastatin, and rosuvastatin, which act by inhibiting cholesterol biosynthesis. In the
treatment process of these patients adverse reactions may occur due to interactions
with medications and foods. Studies involving derivates of fruits from the Amazon
region, such as açaí pulp (Euterpe oleracea Mart.), are rare. To ensure the safety and
effectiveness of treatments, further research is needed. Objectives: The aim of the
present study was to investigate the effect of açaí (Euterpe oleracea Mart.) on the
pharmacokinetics of simvastatin metabolized by CYP3A4 in clinical and in silico studies.
Material and Methods: 12 volunteers received simvastatin on day 1, with a dose of 20
mg orally after a 10-hour overnight fasting. On days 2 to 5, participants ingested 300
mL of Euterpe oleracea pulp, twice a day. On day 6, a dose of simvastatin (20 mg) was
co-administered with the açaí pulp. The biological samples were prepared by the protein
precipitation and detected by UHPLC-MS which provided a good separation of
simvastatin, β,δ-hydroxy acid and the internal standard atorvastatin within 10 min.
Results and discussion: The pharmacokinetic data indicate that the area under the
plasma concentration–time curves (AUC) of simvastatin was decreased by 12,5%. In
silico studies showed that the two main compounds found in açaí (Cyanidin 3-glucoside,
Cyanidin 3- rutinoside) showed inductive activity for CYP3A4, which corroborates the
data obtained in the quantification of blood plasma. Conclusions: In conclusion,
Euterpe oleracea was found to probably inhibit the metabolism of simvastatin in
humans. Based on the food–drug interaction, persons taking daily açaí pulp should be
warned of this interaction possibility.

Introduction: The polymorphisms Arg72Pro (rs1042522) of the TP53 gene and Ile655Val (rs1136201) of the HER2 gene have been linked to susceptibility to different types of cancer and several studies show their association with a higher risk of developing breast cancer. Objective: To investigate the association of Arg72Pro and Ile655Val polymorphisms with the risk of developing breast cancer in women from the city of Macapá, located in the Legal Amazon region, northern Brazil. Material and Methods: 80 DNA samples from women with breast cancer and 83 DNA samples from women without the disease were analyzed. Collected at the Cancer Prevention Institute of Amapá Joel Magalhães - IJOMA and at the High Complexity Oncology Unit (UNACON) of the Hospital de Clinicas Dr. Alberto Lima. Molecular analyzes were performed using the polymerase chain reaction restriction fragment length polymorphism technique (PCR-RFLP). Statistical analyzes to investigate allelic and genotypic frequencies were performed using the R software for the chi-square (X2) and logistic regression by odds ratios (ORs) tests, where a P value less than 0.05 was defined as statistically significant. Results and discussion: The genotypic frequencies for the TP53 gene genotypes were: Arg / Arg 23.7%, Arg /Pro 47.5% and Pro / Pro 28.5% in patients and in controls were Arg / Arg 69.8 %, Arg
/ Pro 19.2% and Pro / Pro 10.8% (X2 = 34,798, p = <0.0001). For the HER-2 gene, the frequency of the genotypes Ile / Ile, Ile / Val and Val / Val, respectively, was 82.5%, 17.5% and 0% in patients and 75.9%, 20.4 % and 3.6% in controls (X2 =63,076, p = <0.0001). The TP53 Arg72Pro and HER-2 Ile655Val gene polymorphisms were statistically associated with the risk of developing breast cancer in women in the city of Macapá. The homozygous Val / Val genotype of the HER-2gene was not observed in the analyzed samples. Conclusion: This study found a significant association between the Arg / Pro and Pro / Pro genotypes for the
rs1042522 polymorphism in the TP53 gene and the Ile / Val genotype for the rs1136201 in the HER-2 gene and the risk of developing breast cancer, suggesting the possibility of using these polymorphisms as a tool to assist in predictive tests for the evolution of breast cancer in diagnosed patients.

Introduction: The demand for tetrazole derivatives has intensified in recent years, as this substance is of great interest at a pharmacological and chemical level. Tetrazolic derivatives are present in drugs such as: Losartan, Valsartan (antihypertensive) and Pranlukast (antiasthmatic). These compounds have many applications in organic synthesis, as intermediates that can be used in reactions involving different reagents in the synthesis of fungicides, in the materials area, pharmacology and can be an alternative for the synthesis of new compounds for use in the fight against several vectors that cause diseases, among which Aedes aegypti, a mosquito of great epidemiological and vectorial importance for world public health, known for transmitting viruses that cause several diseases, such as Yellow Fever, Chikungunya, Rift Valley Fever, Zika and Dengue. Objective: Synthesize tetrazole compounds from Knoevenagel condensation reactions between aromatic aldehyde derivatives and malononitrile, establish the dose-response relationship to the susceptibility of the studied vector and determine the lethal concentrations for 50% and 90% mortality (LC50 and LC90). Materials and Methods: One-pot tetrazole syntheses compounds from aromatic aldehydes, malononitrile and sodium azide derivatives were carried out by microwave radiation and conventional heating. Compounds were identified through Infrared (IR) and Nuclear Magnetic Resonance (NMR) spectra. The tetrazol compounds obtained were evaluated by bioassay procedures according to the guidelines of the World Health Organization (WHO) – Guidelines for Laboratory and Field Testing of Mosquito Larvicides. The results were analyzed with Tukey's test. Results: An optimization was performed for the synthesis of tetrazolic compounds: Reaction without the use of catalysts by microwave radiation and conventional heating, obtaining yields (95 and 94%) and in reaction times of 4 and 24h respectively. Subsequently, the reaction was improved through the use of acid-base catalysts. Was observed that the CuSO4-(Et)3N catalytic system provided a 90% yield in 2 hours of reaction via microwave (MO). Once the best reaction conditions were established, a series of 10 tetrazol compounds were synthesized, showing yields of 85-99%. These compounds were used for larvicidal assays of the Aedes aegypti vector, analyzing that the tetrazolic larvicides 3b and 3c provided the best IC50 and IC90 values.

Perillyl alcohol is a cyclic monoterpene with antineoplastic activity. Its action mechanism is related to the inhibition of the isoprenylation of the Ras protein, responsible for inactivating the p53 protein. The present study aimed to assess the genotoxicity and antigenotoxicity of the perillyl alcohol nanoemulsion through (in vivo) Micronucleus test (MN) applied to peripheral blood erythrocytes of Swiss mice after acute treatment. The perillyl alcohol nanoemulsion was obtained through low energy input with apolar (10%) and polar phases (90%). The animals were divided into groups (6 males each) according to the substance used in the treatment: negative control (water), positive control (doxorubicin), vehicle control (surfactants), genotoxicity test group (test substance nanoemulsion), and antigenotoxicity test group (test substance nanoemulsion associated with doxorubicin). Twenty-four and 48 h after treatment, peripheral blood was collected from the animal’s tail and smeared on a slide for the counting of two thousand polychromatic erythrocytes to perform the Micronucleus test. The nuclear division index was used to determine cytotoxicity. One-way ANOVA with post-hoc Tukey and Student t tests were used to analyze the data. The results of the genotoxicity test in 24- and 48-h samples revealed an increase in the MN frequency in all doses given compared with the negative control (p<0.001), in a time- and dose-dependent manner. The results of the antigenotoxicity test in 24- and 48-h samples revealed no reduction in PCEMN in comparison with the positive control (p<0.001). In conclusion, the perillyl alcohol nanoemulsion induced genotoxicity in a time- and dose-dependent manner, as well as it showed cytotoxic effects.

Nos últimos anos os fungos endofíticos, têm sido alvo de inúmeras pesquisas devido ao seu potencial em produzir metabólitos secundários, especialmente compostos orgânicos voláteis (COVs), com notáveis atividades biológicas. Neste contexto, estes produtos do metabolismo fúngico, vêm sendo caracterizados como nova e promissora fonte de metabólitos biologicamente ativos. Alguns desses efeitos biológicos ainda são desconhecidos pelo homem. Sabe-se que os fungos, emitem uma ampla e complexa variedade de compostos
orgânicos voláteis, principalmente álcoois, aldeídos, terpenos, hidrocarbonetos, compostos de enxofre, etc. Os COVs fúngicos, são utilizados em diversos setores da indústria, e apresentam diferentes aplicações biotecnológicas; como marcadores taxonômicos, micofumigação, aromatizantes e biocombustível. A pesquisa sobre COVs pode contribuir para a descoberta de novos produtos biotecnológicos, com possível atividade farmacológica. Não obstante, a necessidade por novas substâncias e compostos anti-inflamatórios, mais seguros e eficazes e com menos efeitos colaterais, têm se tornado objeto de estudo de inúmeros pesquisadores.
Diante disto, na busca por novos metabólitos secundários de importância farmacêutica, o objetivo deste trabalho é extrair e caracterizar os compostos orgânicos voláteis dos fungos endofíticos isolados dos frutos da Euterpe oleracea e avaliar seu potencial efeito biológico, através de teste anti-inflamatório em modelo experimental Zebrafish (Danio rerio). Os compostos voláteis serão extraídos por hidrodestilação, utilizando aparelho do tipo Clevenger. Após a extração, será realizado a análise química dos compostos voláteis por Cromatografia gasosa acoplada a Espectrometria de Massas (CG-EM). Para avaliar o potencial efeito anti- inflamatório dos compostos voláteis, será utilizado o ensaio de indução de inflamação por carragenina em Zebrafish. A avaliação dos efeitos anti-inflamatórios será realizada por meio de análise comportamental em estágios, observação do edema formado e análise histopatológica. Os resultados encontrados serão utilizados para demonstrar a importância dos metabólitos secundários voláteis produzidos por fungos endofíticos, contribuir para o conhecimento da biodiversidade destes microrganismos, assim como poderão servir de referência para futuros estudos.

Introdução: A doença de Alzheimer é uma doença neurodegenerativa, sendo o tipo de demência mais comum entre pessoas idosas. Neste estudo, as enzimas acetilcolinesterase (AChE) e óxido nítrico sintase (NO) foram selecionadas por serem alvos significativos para drogas terapêuticas. A AChE constitui importante alvo farmacológico em decorrência de seu papel na fisiopatologia da doença de Alzheimer; assim como, a enzima NOS que colabora para o desenvolvimento e progressão da doença. Objetivo: Assim, o objetivo deste estudo foi planejar moléculas de produtos naturais isoladas de plantas medicinais capazes de inibir a atividade enzimática da AChE e NOS para o desenvolvimento de fármacos voltados para o tratamento da doença de Alzheimer. Material e Métodos: Incialmente, foram selecionadas 24 moléculas de produtos naturais da literatura, realizaram-se métodos de modelagem como: estudos de orbitais de fronteira (HOMO e LUMO), mapas de potencial eletrostático, estudo de docking molecular, identificação do padrão farmacofórico, avaliação de propriedades farmacocinéticas (ADME) e Toxicológicas (TOX). Resultados e discussão: Na análise estatística dos descritores o valor mais relevante segundo a correlação de Pearson foi entre HOMO e GAP, apresentando valor igual a 1. Os valores máximo positivo e negativo de MEPs variaram de 0,0871 a-0,11 para a luteolina. Na derivação do grupo farmacofórico, foram alinhadas 9moléculas, contendo três grupos farmacofóricos: dois aceitadores de ligação de hidrogênio e um anel aromático. No estudo de docking, as moléculas estudadas interagiram com o sítio ativo da AChE por meio ligações hidrofóbicas e de hidrogênio, com a NOS por meio de interações de hidrogênio. Na predição farmacocinética e toxicológica, a molécula calebina-A se destacou apresentando o melhor resultado. Dentre todas as moléculas, as que foram mais bem avaliadas em todas as predições, foram: calebina-A, luteolina e quercetina. Com o objetivo de melhorar alguns padrões das estruturas moleculares que obtiveram resultados satisfatórios entre os produtos naturais avaliados, foram feitas 30 modificações planejadas para a estrutura de luteolina, quercetina e calebina-A, sendo 10 análogos para cada uma dessas. Conclusões: O planejamento de análogos destas moléculas apresentou resultados satisfatórios no docking molecular, farmacocinética e toxicidade. Portanto, demonstraram serem análogos potenciais para futuros estudos in vivo e in vitro para o planejamento de moléculas com ação anti-Alzheimer.

Introdução: A ansiedade e a depressão são os transtornos mentais mais prevalentes mundialmente. Elas impactam diretamente na qualidade de vida e na produtividade, especialmente pelo seu difícil tratamento com a farmacoterapia disponível atualmente. Podem acompanhar um indivíduo por muitos anos, gerando grande impacto no fardo global de doenças. A busca por plantas medicinais potencialmente ansiolíticas tem sido uma abordagem relevante no desenvolvimento de alternativas terapêuticas. A catinga de mulata (Aeollanthus suaveolens Mart. Ex Spreng.), uma planta aromática da família Lamiaceae mostrou-se neuroativa, contando com atividades anticonvulsivante, antidepressiva e sedativa em pesquisas utilizando roedores. Assim, o uso de ensaios comportamentais utilizando zebrafish para a avaliação do óleo essencial e sua nano-emulsão visando comparar suas atividades no sistema nervoso central pode fornecer valiosas informações acerca dessa potencial alternativa terapêutica para as doenças mentais comuns. Objetivo: Obter uma nano-emulsão a partir do óleo essencial de A. suaveolens que seja neuroativa e comparar sua atividade ansiolítica após a nano-emulsificação. Metodologia: o óleo essencial foi obtido por hidrodestilação e a partir dele as nano-emulsões foram preparadas por um método de baixo aporte energético. Foram avaliados fatores de influência na geração e estabilização das nano-emulsões, bem como a influência do tempo e temperatura na nano-emulsão selecionada. Ensaios de toxicidade foram realizados utilizando embriões e adultos de zebrafish e a dose letal mediana do óleo essencial foi determinada por análise PROBIT. A comparação da neuroatividade do óleo essencial e sua nano-emulsão foi realizada a partir do ensaio do tanque novo e estudos in silico das substâncias majoritárias foram realizados a fim de predizer os potenciais mecanismos de ação sedativos. Resultados e discussões: Foram obtidas nano-emulsões com aspecto translúcido e azulado pronunciado, associado ao efeito Tyndall evidenteapres entando tamanho médio de diâmetro de gotícula de 70 nm e índice de polidispersão abaixo de 0,2. Esse fitocoloide, utilizada nesse estudo como nano- emulsão selecionada para os ensaios biológicos, não apresentou alterações nos primeiros dias de armazenamento. O teste de performance utilizando embriões de zebrafish permitiu sugerir o aumento da atividade biológica da nano-emulsão comparativamente a atividade observada para o óleo essencial não nano- emulsificado. Em estudos de toxicidade preliminar aguda, a neuroatividade e a intensificação a ação promovida pela nano-emulsificação foi visualizada a partir da indução de hipnose no grupo tratado com a nano-emulsão e apenas sedação no grupo tratado com o óleo essencial não nano-emulsificado. A dose letal mediana total foi de 502,808 mg.kg-1. Aumento semelhante do comportamento exploratório, relacionado à efeito tipo-ansiolítico, foi observado em dose da nano-emulsão selecionada 10 vezes inferior ao óleo essencial não-nanoemulsionado. No entanto, possíveis interferências de agregados de colóides que afetam curvas sigmóide clássicas, efeito sedativo com tendência à hipnose próximo a altas doses e outros fatores podem estar influenciando. Conclusão: Esse estudo abre perspectivas para uso de inibidores da Maturação de Ostwald, incluindo associados ao β-farneseno, considerado um dos possíveis constituintes bioativos, bem como verificação da atuação desses sob a forma livre ou absorção via fusão das nanogotículas com as membranas, com modificação do n e/ou novos aprimoramento do modelo em zebrafish. A mudança do par de tensoativos e redução drástica do tamanho de gotícula, através de técnica amigável ao meio ambiente, contribui para o estado da arte da nanobiotecnologia fitofarmacêutica e desenvolvimento de novos nanofitoterápicos.

Introdução: Em muitos casos de hipertensão arterial, o controle pressórico não é alcançando mesmo com o tratamento sendo realizado adequadamente, podendo ser influenciado por diferentes fatores. A variação interindividual no metabolismo de fármacos é também bastante comum e pouco explorada frente aos casos de resistência terapêutica, sendo, portanto, um dos aspectos a ser considerado na farmacoterapia anti-hipertensiva. O losartana é um dos fármacos mais utilizados para controle da pressão arterial, contudo tanto este como o seu metabólito ativo (EXP3174), apresentam um elevado grau de diferenças interindividuais em seus níveis plasmáticos, os quais podem afetar tanto a eficácia como o surgimento de efeitos adversos decorrentes do tratamento. Para tal, a farmacometabolômica tem sido aplicada na predição das respostas terapêuticas a partir da análise do perfil metabolômico relacionando o uso de fármacos à alterações nos metabólitos em um determinado espaço de tempo. Objetivo: Este estudo objetiva avaliar e correlacionar o perfil metabolômico (plasma e urina) e os níveis plasmáticos de losartana e EXP3174 ao controle dos níveis pressóricos em pacientes hipertensos. Metodologia: Através de um estudo do tipo caso-controle baseado na aplicação de questionário sociodemográfico e clínico para seleção dos pacientes, teste de bioimpedância para obtenção das medidas antropométricas, assim como o monitoramento das concentrações plasmáticas de losartana e EXP3174, mediante Cromatografia Líquida de Ultra Eficiência acoplada a Espectroscopia de Massas sequencial (CLUE-MS/MS). Resultados e discussão: Os achados permitirão determinar a efetividade clínica do tratamento anti-hipertensivo com o losartana e avaliar a correlação das medidas antropométricas e do perfil metabolômico com os níveis plasmáticos e com o controle pressórico alcançado nestes pacientes.

Introdução: A mucosite intestinal é uma complicação comum associada à terapia do câncer, como o uso do quimioterápico cisplatina (CDDP). É caracterizada por dano ao epitélio gastrointestinal que debilita o paciente e prejudica o tratamento. Apesar de sua importância clínica, não existe tratamento até o momento. Na literatura, o óleo de sucupira (OS) (Pterodon emarginatus Vogel) mostrou atividade anti-inflamatória, porém não há relatos para mucosite intestinal. O OS possui caráter lipofílico e viscoso dificultando sua aplicação in vivo. O desenvolvimento de nanoestruturas como as nanocápsulas (NC) representam uma estratégia inovadora para contornar esses inconvenientes. Objetivo: Avaliar a ação de nanocápsulas poliméricas contendo o óleo de sucupira (NC OS) na mucosite intestinal induzida por cisplatina em camundongos. Metodologia: O OS foi caracterizado por cromatografia líquida acoplada à espectrometria de massas. As NC de OS foram produzidas empregando diferentes tensoativos pelo método de nanoprecipitação e caracterizadas físico-quimicamente em relação à distribuição de tamanho e potencial zeta. Os animais foram distribuídos em grupos: Controle (sem mucosite + água), Mucosite (com mucosite + água), Pré-tratado 1 (com mucosite + OS por 7 dias antes e durante a indução da doença) e Pré-tratado 2 (com mucosite + NC OS por 7 dias antes e durante a indução da doença). A mucosite foi induzida através da administração i.p. de 10 mg/kg de CDDP no 5o dia. Para verificar a permeabilidade intestinal, no 8o dia os animais receberam solução de 99mTc-dietilenotriaminopentacético. O íleo foi coletado para análise histológica, dosagem de citocinas (IL-10 e TNF-α) e infiltrado inflamatório (NAG e MPO). Resultados e discussão: O diâmetro médio calculado por espalhamento dinâmico da luz foi inferior a 350 nm e o potencial zeta apresentou valores negativos. NC OS apresentaram adequada estabilidade. O tratamento com NC OS produzidas com os tensoativos Tween e Span na mucosite intestinal demonstrou aumento da permeabilidade intestinal, diminuição de NAG, porém não alterou MPO e as citocinas. Já o tratamento com as NC OS produzidas com tensoativo lecitina, demonstrou diminuição da permeabilidade intestinal, não alterou infiltrado inflamatório, porém aumentou níveis de TNF-α. A avaliação dos tensoativos frente a mucosite intestinal confirmam a piora da inflamação promovida pela administração de Tween e Span devido ao aumento da permeabilidade intestinal e de TNF-α. Conclusão: A avaliação das NC OS produzidas em modelo de mucosite intestinal induzida, apresentou melhora parcial de alguns parâmetros avaliados dependendo dos tensoativos empregados. Contudo, a formulação de NC OS produzida com lecitina promoveu melhores resultados frente a mucosite intestinal quando comparado a OS, sugerindo cautela na escolha de tensoativos em uma formulação.

Introdução: A epilepsia é uma das doenças neurológicas mais comuns no mundo, acometendo em torno de 1% da população mundial. Embora uma gama de medicamentos anticonvulsivantes esteja disponível, aproximadamente um terço dos pacientes não respondem adequadamente aos medicamentos atuais. Objetivo: O objetivo desse trabalho foi avaliar o efeito do Álcool Perílico (AP) sobre convulsões epilépticas in vivo e in silico. Materiais e Métodos: A convulsão foi induzida por pentilenotetrazol (PTZ, 170 mg/kg, i.p.) em zebrafish
adulto, e o anticonvulsivante controle usado foi Diazepam (DZP, 2 mg/kg, p.o.); o AP foi testado nas doses de 10, 50 e 100 mg/kg (p.o.). Para mensurar a convulsão, foram avaliados manualmente comportamentos tipicamente convulsivos, e então, com o auxílio de um software de rastreamento animal (Toxtrac v2.90), os parâmetros motores foram analisados. Por fim, foram executados estudos in silico para elucidar um possível mecanismo de ação envolvido na atividade do AP (structure-based prediction e docking). Resultados e
Discussão: Os resultados mostram que o PTZ induziu o comportamento convulsivo em todos os animais do grupo controle negativo (n = 10), começando com episódios de hiperlocomoção, convulsão propriamente dita e então perda de postura e imobilidade. O DZP inibiu a ocorrência de convulsão em todos os animais do grupo. O AP inibiu a ocorrência de convulsão de forma dose-dependente, com frequências de 90%, 70% e 40% para os grupos tratados com 10, 50 e 100 mg/kg, respectivamente. O tratamento com AP também diminuiu a
frequência e o tempo de perda de postura, a frequência e o tempo de imobilidade induzida por convulsão, o tempo de convulsão, o número de nados em círculo/espiral, e atenuou o déficit motor causado pelas convulsões. A diferença do grupo tratado com a maior dose de AP foi estatisticamente diferente do grupo controle negativo para todos os parâmetros convulsivos avaliados (p < 0,05; Kruskal-wallis). A análise in silico sugere envolvimento do sistema GABAérgico na atividade anticonvulsivante do AP, com predição de inibição da enzima
GABA-AT. Conclusão: Em suma, os resultados sugerem um potencial anticonvulsivante no AP tanto in vivo quanto in silico

Introduction: Parkinson's disease (PD) is the second neurodegenerative disease that affects society, especially in individuals over 60 years of age, and its pathophysiology is characterized by the death of dopaminergic neurons, thus decreasing dopamine production. One of the forms of treatment of PD is the inhibition of monoamine oxidase B (MAO-B), in which recent studies have identified natural products with this activity. One of the safest and fastest ways to study PD is using the animal model ZebraFish, as it has the brain structure of the dopaminergic system with more than 80% compatibility with humans. Objective: Thus, the objective of the study was to design molecules, using in silico methodologies, with MAO-B inhibitory activity, based on natural products, perform the synthesis and test them in vivo. Methodology: A search was made in the literature on natural antiparkinsonian products; subsequently, four were selected for studies, in silico, of pharmacophore derivation, prediction of pharmacokinetic and toxicological properties and molecular docking. With that, it was possible to design three molecules with possible MAO-B inhibitory activity and synthesize them, in order to perform the tests in vivo. Results and discussions: We selected 4 natural products that showed in vitro and / or in vivo antiparkinsonian activity and the drug Selegiline, which was used as a standard molecule for comparison in the in silico study. For pharmacokinetic analyzes, natural products showed satisfactory results and, for the prediction of toxicological properties, natural products showed between low or no toxicity. In docking, molecular all natural products interacted with more than three amino acids from the active site of MAO-B indicating that they have interaction with the enzyme and suggesting the probable inhibitory activity. After the analysis, Amburoside A was selected as a prototype for the modifications and then 3 analogs (PMC1, PMC2 and PMC3) were obtained with a result between average and good synthetic viability and all three showed a prediction of MAO inhibition activity. Later, the prototypes were synthesized, and due to the fact that PMC3 does not have activity studies described in the literature, it was selected for the acute toxicity test in vivo in the Zebrafish model. Conclusions: The planned molecules showed good results in silico, in addition to having good synthetic viability, they also did not manifest toxicity in Zebrafish, being a possible candidate for a safe drug. 

Introdução: A leishmaniose é uma das doenças infecciosas mais importantes do mundo, segundo a OMS. Distribuída em vários países das Américas, temos a Leishmaniose Tegumentar Americana (LTA) causada pela Leishmania (L) amazonensis, que possui uma grande capacidade de causar deformidades, além disso, o tratamento é bastante incômodo ao paciente, o que tem levado à busca por novos fármacos. Objetivo: Diante disso, o objetivo deste trabalho foi avaliar a potencial atividade leishmanicida, frente ao protozoário da LTA, de uma nanoformulação para uso tópico obtida a partir do oleoresina dos frutos de Pterodon emarginatus. Material e métodos: O teste utilizado para o estudo in vitro foi o ensaio colorimétrico de resazurina que avaliou a IC50 de uma nanoemulsão, obtida por um método de baixo aporte de energia, composta por um par de tensoativos (monooleato de sorbitano e o polissorbato 80), OS e água (NEOS5), contra promastigotas de L. amazonensis. O ensaio in vivo avaliou a eficácia da formulação polissorbato 80 (6,26%) monooleato de sorbitano (3,73%), etanol 96% (2%), OS (20%) e água (68%) (NEOS20) em associação a um medicamento de referencia , o antimoniato de Meglumina (Glucantime®), no tratamento de lesões causadas por L. (L) amazonensis em 4 grupos de animais. Resultados e discussão: Após 48h de incubação a NEOS5 apresentou melhor resultado na inibição parasitária com IC50 de 21,83 ± 1,09 ppm, enquanto o OS não encapsulado apresentou IC50 de 32,38 ±3,87ppm. Diante deste resultado seguiu-se para o estudo in vivo, onde observou-se que a lesão com maior redução de tamanho foi a do grupo tratado com a combinação de Glucantime® e NEOS20, com redução de 41%. A lesão passou de 7,4 ± 0,62mm para 4,3 ± 0,88mm durante o período de tratamento, além de apresentar melhor resolução do processo inflamatório e cicatricial, diminuição da carga parasitária na lesão e diminuição dos nivesis de citocinas. Conclusão: A utilização tópica de NEOS20 combinada com Glucantime® apresentou os melhores resultados, melhorando o aspecto geral das lesões e diminuindo significativamente as interleucinas IL10 e IFN-g, indicando uma possível atividade antiinflamatória e cicatrizante da formulação proposta frente ao modelo de leishmaniose tegumentar. 

Introduction: Ellagic acid is a naturally occurring phenolic phytochemical belonging to the group of ellagitannins, which in turn belong to the group of hydrolyzable tannins of polyphenols. The same can be found in plants in their free form, or in the form of ellagitannins, and in the cell membrane. Zeina is a natural polymer whose biological potential has also gained attention. Objectives: To evaluate the cytotoxic, genotoxic, antigenotoxic and histopathological potential of nanoencapsulated ellagic acid by the in vivo test system. Methodology: The method used to determine the cytotoxic effect was determined by calculating the nuclear division index (IDN). To determine genotoxicity and antigenotoxicity, the micronucleus test method was used in peripheral blood cells of male Swiss mice from the Vivarium of the State University of Campinas. For genotoxic evaluation, the animals were treated with nanoencapsulated ellagic acid (ZNP-EA); ellagic acid in free solution (EAS) and blank nanoparticles (BNZp) each solution with a concentration of 5.3 mg / kg p. c .. Peripheral blood samples were collected 24, 48 hours 7, 14 and 21 days for the subchronic treatment. For the antigenotoxic effect, the animals were treated with pre-established concentrations, followed by intraperitoneal injection of doxorubicin - DXR (15 mg / kg p. C.). Results and discussion: The administered substances did not show genotoxic activity compared to the negative control group. However, when administered with DXR they showed an antigenotoxic activity with a reduction rate of 92.01% in 48 hours compared with the positive control group showing that it was able to decrease micronuclei in polychromatic erythrocytes. There was no cytotoxicity in the tested substances and the Histopathological result revealed that there was no toxicity in relation to the liver, spleen, heart and kidney organs. Conclusion: The results reinforce the potential of ellagic acid in combination with zein, providing its great antioxidant and antigenotoxic potential. Key words: Ellagic acid; Nanoencapsulation; Micronucleus; toxicity; Mutagenicity.

Alzheimer's disease (DA) is considered the main and most common agerelated
dementia, accounting for 50-60% of the cases. The most commonly used
pharmacotherapeutic approach for the symptomatic control of DA is the use of
anticholinesterasic drugs, but lately, several research advances in the feeling of proposing
new alternatives, such as multitarget drugs. Objectives: The aim of this study was to
design new candidates for the AChE/BACE1 multitarget inhibitors for the treatment of DA.
Methodology: For this, 17 natural products were selected from the literature with
anticholinesterase activity and 1 synthetic molecule with inhibitory activity for BACE1.
Subsequently, the study of molecular docking was performed using the GOLD software,
followed by derivation of the pharmacophoric pattern in the PharmaGist webserver,
prediction of the pharmacokinetic properties (ADME) with the QikProp module of the
Schrödinger software and toxicological (TOX) by the DEREK software, finally, the hybrid
prototype was designed. Results and discussion: In the study of molecular docking, it
was verified that the selected compounds presented interactions of hydrogen and
hydrophobic with the targets, AChE and BACE1. When performing the derivation of the
pharmacophoric pattern, 9 molecules were aligned presenting 3 pharmacophoric regions:
an aromatic ring, an electron acceptor region and a hydrophobic region. A good result of
the molecules was observed in relation to the pharmacokinetic properties and
toxicological, not presenting mutagenicity and carcigenocity. After the hybridization
process, three hybrid molecules were obtained, which showed inhibitory activity for both
targets. Conclusions: It is concluded that research in the field of medicinal chemistry is
advancing, increasingly towards the discovery of new drug candidates that bring a better
quality of life to patients with AD.
Keywords: Alzheimer's disease; Anticholinesterasic; β-secretase; Molecular modeling.
Acknowledgements: Medicinal Chemistry Laboratory (PharmedChem); Federal
University of Amapá (UNIFAP).

Introduction: The search for pharmacological alternatives to combat obesity is based on the development of compounds that assist in weight loss, being used safely and effectively for a long period. The endocannabinoid system is related to obesity, increasing orexigenic signs and reducing satiety signs. In silico evaluation through
virtual screening and molecular modeling of Cannabis sativa phytocannabinoids for this purpose stems from their polypharmaceutical potential and the existence of synthetic cannabinoid drugs that have already shown this result. Objective: Perform virtual screening based on the phytocannabinoid pharmacophore of C. sativa, to
search for anti-obesity agents with the potential to interact with the cannabinoid receptor 1 (rCB1). Methodology: The virtual screening included the prediction of biological activity, the evaluation of the physico-chemical, pharmacokinetic and toxicological properties of cannabinoids (to obtain a reference pharmacophore) and ZINC molecules, as well as molecular docking in rCB1 (PDB: 5U09). Results and discussion: The pharmacophore obtained revealed a 5-point model, with a hydrogen acceptor region and four hydrophobic regions, and this was submitted to the ZINC server for virtual screening, where 78 molecules were obtained that
signaled antagonistic activity on rCB1, in addition to anti-obesity activity. Among the ZINC molecules evaluated, after analysis of their physical-chemical, pharmacokinetic and toxicological profiles, the ZINC33053402 and ZINC19084698 pointed out as promising anti-obesity agents. Conclusions: The best profile of the ZINC molecules screened to act as an antagonist of rCB1 in peripheral anti-obesity activity were: ZINC33053402 and ZINC19084698 (for presenting a key bond for the blocking of the anandamide endocannabinoid agonist) and high GoldScore. In addition, these molecules have a possible factor favorable to the safety of using a cannabinoid antagonist at the peripheral level, due to their pharmacokinetic profile, which can overcome the barriers of adverse effects inherent to this pharmacological class.

Introduction: Muirapuama (Ptychopetalum olacoides BENTH) is an Amazonian plant used for various therapeutic purposes as well as having aphrodisiac effect, giving it great pharmacological potential. “Green” analytical methodologies have gained strength today as characterize the development and enhancement techniques less harmful to the environment by reducing the use of toxic reagents, time, energy and costs. Such methodologies are essential for the quality control of products with regard to the characterization of phytochemicals aspects of the plant. Objective: To standardize the drying process from the ethanolic extract of Muirapuama root and to characterize it through green analytical techniques. Methodology: Dry extracts were obtained by spray drying first without the addition of adjuvant, then at a ratio of 1: 1 extract/adjuvant. Then the 2³ factorial design was performed to optimize the technological properties of the dry extract. These were characterized by UHPLC, NIR and SEM. Total flavonoid content was expressed as mgEQ (quercetin equivalent) per milligram of extract. Results and Discussions: the drying process was efficient, with higher yield for the 1: 1 sample and samples with higher percentage of added adjuvant. The UHPLC analyzes showed that there is no statistical significance for the factorial design variables, indicating a total flavonoid content compatible with that found in the literature for hydroalcoholic extracts. The developed NIR method is effective in differentiating between dry extracts with and without adjuvant, but not to quantify them. SEM images show that samples with higher concentration of adjuvant have better morphological characteristics and lower moisture absorption rate. Conclusions: It was evidenced that the drying process can be optimized and that the green analytical methodologies optimize the analysis time, generate less residues and can be applied in the quality control of herbal medicines. Keywords: Ptychopetalum olacoides. Green analytical chemistry. Spray drying. Dry extract. UHPLC. NIR. SEM. Muirapuama.

Introduction: nacardic acid is the major compound of cashew nut (Anacardium occidentale L) peel liquid and has been widely studied due to its biological properties, including antimicrobial, antioxidant, anticancer and attenuating cardiomegaly. However, anacardic acid naturally presents as a caustic brown viscous liquid with low solubility in water, limiting its use for biomedical purposes. In order to improve the stability, the functional characteristics of anacardic acid, polymeric nanoparticles were developed in order to enable its pharmacological use. Objective: To evaluate the pharmacological potential of zein nanoparticles loaded with anacardic acid in vitro and in vivo. Methodology: The zein nanoparticles containing anacardic acid were properly developed and characterized, and then subjected to antimicrobial potential evaluation by determining the minimum inhibitory and bactericidal concentration and antibiofilm activity against Staphylococcus aureus and Pseudomonas aeruginosa. They were then subjected to subacute toxicity and genotoxicity testing at the doses of 2.25 and 112.5 orally administered to mice. Finally, the attenuating potential of phenylephrine-induced cardiomegaly at doses of 22.5 and 112.5 µg / kg was evaluated, and its effect was compared to anacardic acid in solution. Results and discussion: The zein nanoparticles loaded with anacardic acid had a size of 381.6 nm, pdI of 0.215, zeta potential of -15.9 mV, and remained stable over 90 days. Its bacteriostatic (49 ng/ml) and bactericidal (196 ng/ml) action against S. aureus and only bacteriostatic action (> 3.125 ng/ml) against P. aeruginosa at very low concentrations has been demonstrated. They were more efficient in reducing the viability of bacterial biofilms than anacardic acid in solution. No relevant signs of subacute toxicity or nanoparticle-related genotoxicity were observed at the doses tested. Nanoparticles at the lowest dose (22.5 µg/kg) were more efficient in attenuating induced cardiomegaly compared to the highest dose and equivalent anacardic acid in solution. Conclusions: Nanoencapsulation of anacardic acid in zein nanoparticles was successfully performed, improving its biological properties, achieving important pharmacological effects at extremely low doses, which did not show relevant signs of toxicity, which demonstrates its innovative pharmacological potential as an agent. antibacterial or noticeably attenuating cardiomegaly, as there is no specific treatment available.

Introduction: The biological evolution of bacteria to antibiotics represents a condition that implies a shelf life for these drugs, as they are static molecules and lacking the evolutionary capacity of bacteria. Against this background, bacteriophages (bacteria-infecting viruses) are natural bacterial predators, with therapeutic and biotechnological potential for bacterial control, with the advantage of co-evolving with bacteria. The characterization of these viruses is one of the first steps for their use in therapeutics and biotechnology for the control of pathogenic bacteria Objective: To characterize bacteriophages isolated from sewage and evaluate their lytic activity against pathogenic bacteria. Methodology: Microbiological enrichment and viral isolation assays, host range analysis, viral filtrate storage stability at 4 ° C analysis, transmission electron microscopy assays for viral classification, and EcoRI and HindIII enzyme restriction assay for RFLP molecular differentiation between the isolated. Results and discussion: Two phages from the Siphoviridae family (vB_EcS_LMPC and vB_EcS_IPC) and one from the Myoviridae family (vB_SaM_NLFC) were isolated, all with polivalent host range, stable to the storage as filtrates at 4 ° C  for more than six months. Also being detected five phages belonging to the Myoviridae family obtained with Escherichia coli, and a filtrate obtained with Staphylococcus aureus, it was not possible to detect viral particles by transmission electron microscopy and assure it solation status. the molecular assays with Eco RI and HindIII revealed ds DNA in all the samples, corroborating with the viral taxonomy data obtained;  The analysis and comparison of the results obtained with those in the literature suggest that the phages obtained are jumbo type. Conclusion: The isolates and the filtrates obtained display very large viral particles and have potential applicability to the antibacterial therapy, as well as to bacterial biocontrol for some industrial applications, but further characterization studies and application tests should be conducted.

Introduction:Medicinal plants are often used by the population to treat a variety of conditions, and this improvement is usually associated with secondary metabolites, which may be pharmacologically active. However, it is important to understand that these organisms may vary in their chemical composition to the detriment of environmental factors such as seasonality and precipitation, which consequently positively or negatively influence biological activity. Objective: In this sense, the present work aimed to evaluate the seasonal variation of chemical composition and antioxidant activity of extracts of leaves of Croton cajucara (Sacaca), stem bark of Dalbergia monetaria (Verônica) and Licania macrophylla (Anauerá). add value to these vegetables that are widely used in the Amazon. Methodology: Using methodologies such as quantification of phenolic compounds (phenols and total flavonoids) by spectrophotometry, and to evaluate the antioxidant activity through DPPH (2,2-diphenyl-1-picrilhydroxyl), FRAP and Phosphomolibdenum methods. For this, monthly collections were performed over a period of twelve months, from the same individual of each species studied and the data were represented in graphs and tables and treated by ANOVA methods followed by Tukey and pearson correlation. Results and discussions: C. cajucara presented high rates of phenols and total flavonoids in June with strong correlation (r = 0.89), however, both showed weak and negative correlation with precipitation; Rain correlated moderately only with FRAP and Phosphomolibdenum, but negatively. D. monetaria showed better (higher) results for chemical composition and antioxidant activity than the other species analyzed, with emphasis on the less rainy period which showed the highest concentrations; phenols and flavonoids correlated moderately with each other (r = 0.38) and weak and moderate correlated with precipitation; Rain presented a strong negative correlation with Phosphomolibdenum (r = -0.65). For L. macrophylla, there was no correlation between phenols and flavonoids (r = 0.09) and rainfall moderately correlated only with DPPH (r = 0.36). Conclusions: Seasonal variation occurred during the analyzed season for the three studied species, some more accentuated and others less. Precipitation influenced little more and more negatively.

Introduction:Medicinal plants are often used by the population to treat a variety of conditions, and this improvement is usually associated with secondary metabolites, which may be pharmacologically active. However, it is important to understand that these organisms may vary in their chemical composition to the detriment of environmental factors such as seasonality and precipitation, which consequently positively or negatively influence biological activity. Objective: In this sense, the present work aimed to evaluate the seasonal variation of chemical composition and antioxidant activity of extracts of leaves of Croton cajucara (Sacaca), stem bark of Dalbergia monetaria (Verônica) and Licania macrophylla (Anauerá). add value to these vegetables that are widely used in the Amazon. Methodology: Using methodologies such as quantification of phenolic compounds (phenols and total flavonoids) by spectrophotometry, and to evaluate the antioxidant activity through DPPH (2,2-diphenyl-1-picrilhydroxyl), FRAP and Phosphomolibdenum methods. For this, monthly collections were performed over a period of twelve months, from the same individual of each species studied and the data were represented in graphs and tables and treated by ANOVA methods followed by Tukey and pearson correlation. Results and discussions: C. cajucara presented high rates of phenols and total flavonoids in June with strong correlation (r = 0.89), however, both showed weak and negative correlation with precipitation; Rain correlated moderately only with FRAP and Phosphomolibdenum, but negatively. D. monetaria showed better (higher) results for chemical composition and antioxidant activity than the other species analyzed, with emphasis on the less rainy period which showed the highest concentrations; phenols and flavonoids correlated moderately with each other (r = 0.38) and weak and moderate correlated with precipitation; Rain presented a strong negative correlation with Phosphomolibdenum (r = -0.65). For L. macrophylla, there was no correlation between phenols and flavonoids (r = 0.09) and rainfall moderately correlated only with DPPH (r = 0.36). Conclusions: Seasonal variation occurred during the analyzed season for the three studied species, some more accentuated and others less. Precipitation influenced little more and more negatively.

INTRODUCTION: The search for biological methods to obtain metallic nanoparticles is highlighted due to the diverse biotechnological applications, these procedures appear as alternative to traditional, physical and chemical methods. OBJECTIVE: Biosynthesis of silver metallic nanoparticles (AgNP) and copper (CuNP) by endophytic fungi isolated from Bertholletia excelsa (Brazil nut) almonds from Amazonia. METHODOLOGY: An initial screening with six endophytic fungi was carried out: Aspergillus sp. (Biorg 5), Trichoderma sp. (Biorg 7), Phaeoacremonium sp. (Biorg 15), Rhizopus sp. (Biorg 16), Aspergillus sp. (Biorg 22) and Clamidosporium sp. (Biorg 36), an experimental design was used to obtain the best AgNps biosynthesis conditions for the fungus that produced Nps in smaller size. For the CuNPs, different co-substrates were used: NpBP, NpEtOH, NpGly and NpAsc, followed by infrared characterization with fourier transform, besides evaluating the effects of copper on the growth and morphology of Phaeoacremonium sp. RESULTS AND DISCUSSION: after screening with endophytic fungi, Phaeoacremonium sp. (Biorg 15) produced AgNPs up to 44.06 nm in size. The characterization of AgNPs by FTIR suggests interactions between the phosphate cofactor and mycelial components of the fungus Phaeoacremonium sp. with AgNPs. The silver NPs showed antibacterial activity against the strains Staphylococcus aureus (ATCC33591), Staphylococcus epidermidis (ATCC12228), Proteus mirabilis (ATCC 15290) and Klebsiella pneumoniae (ATCC 4352) and the ecotoxicity tests on microalgae Chlorella vulgaris showed high toxicity in concentrations (10 mmol and 0.001 mmol). Regarding the CuNPs, the results showed that the co-adjuvant phosphate produced CuNPs of 66.84 dm with -34 mV zeta potential. The FTIR analysis corroborates the formation of CuNPs. In the case of growth analysis of halo in solid medium in the presence of the metal, there was slight deformation in the growth of Phaeoacremonium sp. While in the absence of the metal, no morphological effect was observed.CONCLUSIONS: The endophytic fungi isolated from Bertholletia excelsa were able to produce AgNPs at CuNPs in sizes ranging from 50-300 nm as a viable alternative, low cost, no addition of toxic agents and mild conditions, and demonstrate potential biocides against bacteria and toxicity in microalgae C. vulgaris. While to obtain the CuNPs the reducing agents played the role of cappers and protectors.

ajiocaica

Introduction: Pogostemon cablin (Blanco) Benth, popularly known as Oriza and Patchouli is a plant of the family Lamiaceae, which has several biological activities including antimicrobial, antioxidant, analgesic, anti-inflammatory, antithrombotic, antidepressant, cytotoxic and recognized entomotoxic potential that serve as alternative strategy for the chemical control of Aedes aegypti. Objective: To carry out the chemical study and evaluation of the antioxidant, cytotoxic, antimicrobial and larvicidal activity of the essential oil and crude ethanolic extract of P. cablin. Methodology: The identification of metabolites was performed by phytochemical tests, quantification of total phenolics for extracts, and GC-MS for essential oil. The larvicidal activity was performed against the larvae of A. aegypti. The antioxidant activity was evaluated by the sequestering ability of 2,2-diphenyl-1-picryl-hydrazyl (DPPH). As for the microbiological evaluation, the technique of dilution in microplates against three bacteria was used. The cytotoxic activity was evaluated against larvae of Artemia salina. Results and discussion: The species P. cablin presented the following major compounds in the essential oil: patchouli alcohol (33.25%), Seyshellene (6.12%), α-bulnesene (4.11%), Pogostol 33%) and Norpatchouleno (5.72%), in the extract the classes of compounds: steroids and triterpenoids, depsides and depsidones, which in synergy with the other substances potentiated the significant larvicidal action of the species with LC₅₀ of 28.43 μg.mL^-1 for oil, and LC₅₀ of 63.91 μg.mL^-1 for the extract, in 24 h. There was no antioxidant activity, however, the essential oil presented antimicrobial activity against all bacteria tested with MIC and CBM of 62.5 μg.mL^-1 and the extract showed inhibition of bacterial growth against E. coli with MIC of 31.25 μg.mL -1 . The essential oil showed a significant LC₅₀ toxicity of 24.25 μg.mL^-1 and the moderate extract LC₅₀ toxicity of 257.93 μg.mL-1. Conclusions: The P. cablin species showed a significant larvicidal potential with antimicrobial action, absence of antioxidant action and high toxicity.

Introduction: The therapeutic monitoring of Losartan and its metabolite by bioanalytical methods in chronic renal patients aims to promote the posologic individualization and optimization of pharmacological treatments, as well as to prevent invasive therapies and to guarantee patient safety. Objective: The aim of this study was to evaluate the pharmacotherapeutic profile of ambulatory kidney patients at a public hospital in amapá, in addition to developing and validating a method by Liquid Chromatography of Ultra Efficiency coupled to sequential Mass Spectroscopy (UHPLC-MS/MS) for quantification of Losartan and its active metabolite for plasmatic monitoring in kidney chronic patients. Methodology: At the first moment, we obtained data on comorbidities and medications used by the patients, resulting in hypertension as main comorbidity and Losartan as the most frequently used medication, being the same and its active metabolite (Losartan Acid) selected for the development of method able to monitor their concentrations in human plasma. Blood was collected from five chronic renal patients who were taking Losartan. The developed method was validated analytically and bioanalytically for the plasma matrix. Results and discussion: The method presented linearity, precision, accuracy, sensitivity, robustness, extraction efficiency and selectivity for the concentration ranges from 0.005 - 1 μg/mL for Losartan and 0.001 - 6 μg/mL for Losartan. In the application of the method in the patient samples, it was observed that two patients presented subtherapeutic levels of Losartan and the metabolite after administration of maintenance dose, demonstrating the need to monitor this antihypertensive administered to renal patients for control of blood pressure, and ensure efficacy and safety in pharmacological treatment. Conclusion: Therefore, efficient and sensitive method was presented, enabling the implementation of clinical protocols for the
monitoring of Losartan

Introduction: Dyslipidemias are metabolic alterations of lipids which induce increased serum lipoproteins, cholesterol, and triglycerides, being a risk factor for the development of atherosclerosis.Objective: This study aimed to assess the effect of Rosmarinus officinalis’ essential oil (ORO), and its nanoemulsion (NEORO) on dyslipidemia induced by Triton and Cocos nucifera saturated fat (GSC) in Wistar rats. Methodology: To induce dyslipidemia was performed treatment either with 2 mL of GSC or Triton at 150 mg/kg. In both models, animals were treated with ORO (100 mg/kg) and NEORO (500 μg/kg). Then, blood samples were collected for biochemical analysis; after animals were euthanized, their organs and abdominal fat were removed for analysis, and the aorta was assessed through MEV for atheromatous processes. Statistical analysis was performed using the software GraphPad Prism (7.0), values were represented as a mean and standard deviation. Results and Discussion: In the phytochemical evaluation of ORO, the major compounds detected by gas chromatography coupled to mass spectrometry (GC-MS) shows the presence of α-pinene (8.13%), limonene (21.99%), 1,8-cineole (33.70%), and camphor (27.68%). Triton-induced dyslipidemia led to a significant increase of total cholesterol, LDL, and triglycerides. Groups treated with ORO and NEORO had a significant decrease in total cholesterol, LDL, and triglycerides, just as the group treated with simvastatin (SIN). GSC-induced dyslipidemia resulted in an increased amount of abdominal fat, hypercholesterolemia, hyperglyceridemia, increased levels of LDL, and atheromatous process formation in the aorta. All treated groups (ORO+GSC, NEORO+GSC, SIN+GSC) had a significant decrease of hypercholesterolemia, hyperglyceridemia, abdominal fat, and inhibition of atheromatous process formation in the vascular endothelium.Conclusion: The results reported in this study evidence that treatment either with ORO or NEORO exerts anti-dyslipidemic and anti-atherogenic effects in the tested models.

Introduction: Anemia, characterized by low concentration of hemoglobin levels, is caused by several factors. Iron deficiency anemia is the most common and especially affects children and adolescents, women of childbearing age and pregnant women due to the high iron requirements. MTHFR helps maintain the pool of folate and methionine, avoiding the accumulation of homocysteine. Patients with elevated levels of homocysteine have a wide range of clinical features. Cysteine is a protein derived from the metabolism of homocysteine and is related to the regulation of iron in the body. Objective: To identify the A1298C polymorphism of the MTHFR gene in patients with iron deficiency anemia, compared with socioeconomic data. Methods: We analyzed the genetic polymorphism of the blood samples from the blood donors who were part of the control group and the patients with HEMOAP iron deficiency anemia through PCR and electrophoresis techniques. We also applied a socioeconomic questionnaire. The same questionnaire was applied to the control group and to the patients who agreed to participate in the study through the signing of the Informed Consent Term. Samples and hematological data of the patients were obtained by authorization of HEMOAP with the signature of the Term of Consent. Results and Discussion: In a total of 42 patients, 21 (50%) had the AC genotype, 5 (12%) CC genotype and 16 (38%) normal AA genotype. Regarding the socioeconomic data, the majority of the patients presented low family income and with education level up to high school completed. Conclusion: Through the results of the molecular analyzes and the comparison with the questionnaire data presented in the tables, it can be concluded that the A1298C polymorphism of the MTHFR gene and the social and economic characteristics may contribute to the development of iron deficiency anemia.

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-Introdução: O uso do filme de quitosana em aplicações biomédicas tem um grande potencial terapêutico, devido as suas boas propriedades que incluem biodegradabilidade e atividade antimicrobiana. Objetivo: Assim, o objetivo foi de avaliar os efeitos do glicerol, incorporado ao biomaterial, sobre a molhabilidade e a flexibilidade do filme de quitosana. Metodologia: Foram preparados por casting, filmes sem glicerol e filmes contendo 3,125%, 6,25% e 25% (p/p) de glicerol. Em seguida, foram realizadas medidas de espessura; medidas de ângulo de contato; medidas de propriedades mecânicas; caracterização morfológica por Microscopia Eletrônica de Varredura (MEV) e Microscopia de Força Atômica (AFM); análises de Espectroscopia no Infravermelho e Difratometria de Raio X, além de testes de sorção e solubilidade em água. Todos os resultados comparados através de análise de variância (ANOVA), seguido por Teste de Tukey (p<0,05). Resultados e discussões: Apenas a espessura do filme contendo 25% de glicerol apresentou diferença significativa em relação à amostra padrão. Todas as amostras apresentaram grande capacidade de sorção e baixa solubilidade em água. As medidas de ângulo de contato indicaram que a molhabilidade do filme aumentou com o aumento da concentração de glicerol. Os resultados da Nanoindentação indicaram que a flexibilidade do filme melhorou com a adição de plastificante. As imagens de MEV revelaram uma estrutura interna fibrosa em forma de placas, enquanto que as topografias por AFM denunciaram a superfície nanoporosa e irregular dos filmes de quitosana, sendo que a rugosidade diminuiu com o aumento da concentração de glicerol. Os espectros e os difratogramas dos filmes obtidos mostraram que a adição de glicerol não modificou significativamente a estrutura química do filme de quitosana. Conclusões: O filme de quitosana com 25% de glicerol foi o que apresentou melhores características para uma possível aplicação na área biomédica, sendo o mais molhável e flexível entre todas as amostras.

Introduction: The synthesis of fatty amides is an important branch of organic chemistry that aims to develop new substances with bioactive characteristics and pharmacological applications such as antifungal, fungicide, anti-inflammatory cosmetics, among others Objectives: The objective of this work was the chemical synthesis of an amide compound derived from the esterified fatty acids present in the patauá oil and to analyze its effectiveness in combating strains of bacteria Staphylococcus aureus (ATCC 33591). Methodology: The fatty amides were synthesized using 3 ml of patauh oil and 1 mL of solvent-free isopropylamine, varying the types of catalysts between CAL-B, TiO2, SiO2 and Al2O3 - 10 mg in individual reactions, for 24 hours at room temperature (27 ± 2 °C). The compounds were characterized by Nuclear Magnetic Resonance (NMR) of Carbon 13 - 13C, Mass Spectrometry (GC - MS) and Infrared (IV) with Fourier Transform. The antimicrobial tests were carried out in vitro against the Staphylococcus aureus strain (ATCC 33591), being tested in natura form, OP (patauá oil), EE (ethyl esters of patauá oil), and AG (amide grease) , with positive control of vancomycin. Results and discussion: Among the conditions studied, the results of direct and solvent-free amidation presented higher yield when 5% of Al2O3 was used as catalyst, with a conversion of 94% at 24 h of reaction when compared to CAL-B lipase that yielded 82% conversion after 24 h. After the spectroscopic characterization, AG antimicrobial tests against Staphylococcus aureus (ATCC 33591), showing a MIC activity of 1.9612 mg / mL while the ES with MIC of 3.4125 mg / mL. Conclusions: The solvent-free amidation process proved to be advantageous in relation to the described literature, where the products obtained showed relative activity against the selected microorganisms, thus being considered a viable and innovative synthesis.

The Aedes aegypti mosquito has been a public health problem worldwide as one of the main transmitters of dengue, zika, chikungunya and yellow fever. The control of A. aegypti is realized mainly by the application of synthetic chemical pesticides, some with high toxicity, which has been caused adverse impacts on human health and damages on biodiversity. Therefore, natural products and their derivatives are being used in the control of A. aegypti larvae, thus, flavonoids arise as an alternative potential in the development of products for vector control. Objectives: In this sense, the objective of this work was to analyze the physical properties of complexes derived from rutin and to carry out the development of larvicidal activity against larvae of the Aedes aegypti mosquitoes. Methodology: Initially, the rutin-Zn (II) complex was synthesized mixing dropwise a methanolic solution of Zn(CH3OO)2.2H2O (0.4 mol.L-1) with a methanolic solution of rutin (0.1 mol L-1). The mixture was stirred at 300 rpm for 24h at a temperature of 37-40 °C and subsequently the complex was vacuum filtered. Then its physics properties were determined by FT-IR, UV-Vis, DRX and DLS spectroscopies. The larvicidal activity was evaluated against Aedes aegypti mosquito larvae by exposure to different concentrations of formulations containing the metal complexes compared to the free rutin in 24h and 48h. Results and discussion: FT-IR UV-Vis and DRX analyzes indicated the formation of a Rutin- Zn complex with possible binding sites in the system between the ring C carbonyl and the 5-OH group and the dihydroxyl groups 3'-OH and / or 4'-OH evidenced by chemical shifts observed in these measurements. The DLS study showed that the complexes presented higher average particle size and higher polydispersion index (Pdi) than the ligand, expected values due to formation of the complexes, these measurements indicated good homogeneity in the distribuition of the particle size of the Zn-rutin complexes. The data from the biological assay suggest that the complexes obtained an increase in larvicidal activity against Aedes aegypti larvae, presenting better LC50 and LC90 values for 24h and 48h compared to rutin. Conclusions: From the results obtained, it was possible to conclude that this work was promising for the study of new larvicidal agents based on flavonoid-metal, providing good perspectives for the control of larvae with an ecofriendly approach to the environment.
Keywords: Flavonoid. Metal complex. Rutin-Zn (II). Larvicidal activity.

Introduction: Viral diseases transmitted by vectors such as Aedes aegypti (Diptera Culicidae), constitute an important public health problem in Brazil. The use of synthetic chemical insecticides in vector control demonstrates environmental toxicity and causes resistance to mosquitoes. It is observed the need to develop insecticides of natural origin in order to avoid the use of these substances and reduce environmental toxicity. Quercetin is flavonol widely found in foods and has many biological activities. Its actions against certain pests, can be considered an alternative for the control of A. aegypti. However, its low aqueous solubility makes it difficult to produce a water-dispersible product, where the larvae of the mosquito develop. Objective: This work aim to produce quercetin nanosuspension (NS-QUE) and evaluateits the toxicity in A. aegypti larvae compared to its bulk form (QUE). Thus it also evaluate its environmental impact on algae of the species Chlorella vulgaris. Methodology: NS-QUE was prepared by solvent displacement method followed by evaporation. The physico-chemical characteristics were monitored for 30 days. The efficacy of NS-QUE and bulk QUE was performed against A. aegypti larvae for 240 h with concentrations of 100 ppm, 175 ppm, 250 ppm, 375 ppm and 500 ppm and the larval morphology was performed by scanning electron microscopy. Results: NS-QUE were successfully obtained by a low energy method cost technique. NS-QUE and bulk QUE demonstrated toxic effect against the larvae, especially the nanosuspensions. A superior larvicidal activity of NS-QUE was observed when compared to its bulk form, especially in high concentrations. No environmental toxicity was observed for concentrations tested with NS-QUE. Conclusion: These data may contribute to the future use of NS-QUE as a promising candidate for the control of vectors such as A. aegypti, since they present a selective toxic activity in the larvae.

O uso de plantas medicinais é comum como alternativa no tratamento de algumas doenças que acometem a população. Tem-se como exemplo, a espécie Spondias mombin que é utilizada popularmente para o tratamento de várias doenças, dentre elas, transtornos neuropsiquiátricos. Apesar do uso dessa planta ser frequente, são escassas as pesquisas que avaliem a segurança de sua utilização como medicamento, assim como a toxicidade da mesma. Objetivo: Dessa forma, o objetivo deste trabalho foi avaliar os efeitos tóxicos agudos, a atividade ansiolítica e antidepressiva do extrato hidroetanólico das folhas de Spondias mombin (EHEFSm) em Danio rerio (zebrafish). Metodologia: A toxicidade foi avaliada determinando-se a concentração letal (CL50) e a dose letal (DL50). A atividade ansiolítica foi avaliada no teste de preferência claro/escuro e, a atividade antidepressiva pelo teste de mergulho em tanque novo. Resultados e discussões: Na avaliação da atividade ansiolítica, os resultados dos parâmetros observados mostraram que o extrato apresentou atividade similar a do controle positivo (buspirona) nas duas vias de administração (imersão e oral) na concentracão de 25 mg/l e com a dose 25 mg/kg. Na avaliação da atividade antidepressiva, os resultados obtidos pela avaliação dos parâmetros apontaram que o extrato demonstrou atividade semelhante ao grupo controle positivo (fluoxetina) nas duas vias de administração utilizadas no teste. A exposição por imersão com as diferentes concentrações do extrato (25, 50 e 75 mg/l) permitiu a determinação de CL50 que foi de 49.86 mg/l. O tratamento por via oral com as diferentes doses (1, 3, 5, 7 e 9 g/kg) possibilitou a determinação da DL50 que foi de 4,515 g/kg em 48h. Os resultados evidenciaram que as doses utilizadas nos testes de ansiedade e depressão não foram tóxicas, não apresentando alterações histopatológicas. Conclusão: A partir desses resultados é possível sugerir que o uso das folhas de Spondias mombin na medicina popular para o tratamento de transtornos neuropsiquiátricos foi evidenciado neste estudo.

Introduction: The species Acmella oleracea (L.) R.K. Jansen (Asteraceae), known as jambú, has several established pharmacological activities and literature data demonstrate its efficacy in sexual disorders. Objectives: To evaluate the effects of oral administration of the hydroethanolic extract of A. oleracea flowers at doses of 88.91 mg / kg (G2) and 444.57 mg / kg (G3) on systemic toxicity and fertility on Wistar rats. Methodology: The extract obtained was analyzed by gas chromatography coupled to mass spectrometry and then used in biological assays. Evaluation was performed at 90 days of age for both sexes and the treatment period for females from 104 to 124 days of life and for males from 90 to 120 days of life. Measurements of feed intake, water intake and weight, estrous cycle (females), sexual behavior (males), reproductive parameters, biochemical and hematological (female), hormonal (male), sperm (male) and histopathological (females). Results and discussion: Gas chromatographic analysis detected (2E, 6Z, 8E) -N-isobutyldeca-2,6,8-trienamide as major compound of the extract (84%). The extract did not cause toxicity in females, and in estrous cycle it was observed that the frequency of the fertile phases increased, whereas the non-fertile phases showed a significant reduction in the animals treated with the EHAo in relation to the control. There was a significant increase in water intake (p <0.01), triglyceride levels, total cholesterol and fractions (p <0.05) and neutrophil percentage (p<0.05). In males, treatment did not cause toxicity, improved sexual behavior and increased hormone levels (p <0.001) at both doses. Conclusion: The treatment with EHAo is safe in the concentrations and time of treatment studied, being able to influence the estrous cycle, without altering the folliculogenesis in females and in males increases the libido without affecting the spermatogenesis.

Introduction: Euterpe oleracea is a Brazilian palm species and its fruits are commonly known as açaí. The oil extracted from açaí fruits is chemically comparable to olive oil, being oleic acid considered its main constituent. Despite the great potential of açaí, to our knowledge, it remains almost unexplored concerning obtainment of nanoemulsions with its lipophilic fraction.Objectives: Therefore, the purpose of this study is to develop oil-in-water nanoemulsions from açaí fruits.  Methodology: The transesterification reaction catalyzed by lipase from Candida antarctica (CAL-B) was used for characterization of the fatty acids present in the sample and oleic acid was the main compound. Anthocyanins were also found in the lipophilic fraction. Nanoemulsions were prepared using different methods, using organic solvent or heating or organic solvent-free/non-heating methods.  Results and discussion: Several formulations were obtained by changing surfactant nature. Lower mean droplet size (184.7 ± 0.92 nm) and narrow distribution (polydispersity index = 0.218 ± 0.003) was observed using polyethylene glycol 400 dioleate 1% (w/w, expressed as surfactant content at former aqueous phase) in the organic solvent method. No phase separation, satisfactorily particle size distribution (mean droplet size = 313.3 ± 8.84 nm and polydispersity index = 0,400 ± 0,036) and zeta potential (-37.4 ± 0.551) were observed for the nanoemulsion prepared with polysorbate 80/sorbitan monooleate (HLB 11) in the organic solvent-free/non-heating method. Conclusions: The present study allowed a critical understanding of some aspects of nanoemulsification of the lipophilic fraction from Euterpe oleracea O/A nanoemulsion. Thus, this study it contributes to valorization of acai oil and development of potential phytopharmaceuticals innovative nanoproducts with this natural Amazon raw material.

Chronic Kidney Disease (CKD) is characterized by slow, progressive and irreversible loss of renal functions, which may result in adaptive processes that keep the patient asymptomatic. For patients who maintain at least 10-15% of normal renal function, treatment is performed with medications and appropriate diet. When renal function is further reduced, it is necessary to use other treatment methods, such as hemodialysis. Therefore, the objective of this study was to evaluate the risks associated with medications and to conduct a pilot study of the implementation of the pharmaceutical care service at the Nephrology Unit of Amapá, the only hemodialysis clinic available through the Unified Health System in the state. One-hundred fifty-six patients on dialysis were interviewed to assess the risks associated with medications, outlining their sociodemographic profile and identifying Potentially Inappropriate Medications (MPIs) and potential drug interactions. It was observed that the majority of the patients were male and hypertensive. The consumption of drugs among women was higher. There was a positive association between the number of drugs used and the presence of drugs with potential risk to the clinic and the presence of potential drug interactions. The prevalence of risks was related to the presence of hypertension. Subsequently, 16 patients were selected to participate in the pilot study of implementation of the Pharmaceutical Care service, using the Pharmacist's Work-up of Drug Therapy method. Eighty-six Drug-Related Problems (DRPs) were identified during the follow-up period (seven months), especially those related to non-compliance. The interventions were mostly related to monitoring and dosage adjustment and were considered significant to their impact on therapy. At the end of follow-up, an improvement was observed in blood pressure and hemoglobin dosage, which are essential in the control of hypertension and CKD. It is concluded that the assessment of risks related to drugs is an important tool in the care of patients to develop risk prevention strategies and to support the conduct of Pharmaceutical Care. The implementation of this service was able to contribute to the prevention and resolution of DRPs, improvement of clinical and laboratory parameters, helping to recover the health of patients with nephropathy.

Alzheimer's disease (AD) is a progressive degenerative disease, the most common type of dementia incident on the population over 60 years of age. The strategy further applied in the treatment of patients with DA is targeting the cholinergic pathway, which involves the use of drugs with inhibitory effect on the biological function of the enzyme acetylcholinesterase (AChE). However, this strategy is not very effective. GSK-3β enzyme is associated with hyperphosphorylation of tau protein which destabilizes microtubules in cell and leads ultimately result in neuronal cell degeneration, being a promising target in actuality, may be more effective than current cholinergic alternative. The aim of this study was to propose new candidates to GSK-3β enzyme inhibitors. For this, 40 inhibitors were selected from BindingDB database, molecular modeling calculations using various chemical-quantum descriptors selected using a Pearson correlation matrix, the pharmacophore profile search, screening ADME / Tox, electrostatic potential maps, orbital border (HOMO and LUMO), beyond docking simulation and prediction activity and synthetic feasibility of new potential GSK-3β enzyme inhibitors. In descriptors calculations, the quantum-chemical parameters calculated at B3LYP/6-31G **, more relevant according to Pearson correlation due to the IC₅₀ value were: LUMO + 1; Softness Molecular and LogP with values of 0.4326; 0.4450 and 0.4248, respectively. The HOMO of CID44219658 inhibitor is in the imidazole pyridine ring and the part of the pyrrole and the LUMO is on the aromatic ring of the C-C bond six carbons. The maximum positive and negative values of MEPs ranged from 0.101155 ua (CID 6639576) at -0.09879 ua (CID 44219658). The pharmacophoric region was expected to 5 aromatic rings, two hydrogen bond acceptor, one hydrogen bond donor and a positive region. No inhibitor showed blood-brain barrier permeability. Among the 40 selected inhibitors, the substance CID 44219658 has the lowest IC₅₀ value, and then used as a prototype for proposing modifications molecular, they obtained four proposals. The predictions of ADME properties, all proposals had a good profile of absorption and distribution. The four proposals have values of Pa> Pi (Proposal 1: Pa = 0.363, Proposal 2: 0.172; Proposal 3: 0.180 and proposal 4: Pa = 0.180), thus indicating the biological activity for GSK 3β, furthermore, the proposed indicate averages synthetic accessibility structures. Based on these results, the proposed one (3-(5-chloro-1-benzofuran-7-yl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione) is possibly the most promising, indicating the possibility of study for evaluation of biological activity in vitro and in vivo.

Studies using microalgae for a variety of purposes have been growing significantly in recent years. Its biotechnological potential and the advantages of cultivation compared to other raw material vegetables were the main factors that triggered these researches, highlighting the high productivity of molecules corresponding to carbohydrates, proteins and lipids, of these especially fatty acids, organic components used in the human diet, usually employed in the pharmaceutical and food industry. Thus, the present work aimed to determine the profile of the fatty acids produced by microalgae and cyanobacteria collected and identified in aquatic environments of the city of Macapa-AP. For this, fourteen species were collected, isolated and identified, among these twelve were analyzed by Infrared Spectrometry - Fourier Transformed and identified the main functional groups present in the samples. In front of that, considering the species Scenedesmus ecornis with high biomass productivity, it was chosen to evaluate the best method of lipid extraction. The method by magnetic stirring using a chloroform-hexane solvent mixture was more efficient (40.6 ± 3.03) in crude lipid extraction when compared to Soxhlet extraction (10.66 ± 1.02), followed by hexane and chloroform solvents. Both by acid catalysis (sulfuric acid) and by enzymatic catalysis (Candida antarctica lipase) using the hydrolysis followed by esterification and transesterification it was possible to identify ethyl esters of fatty acids (palmitic, linoleic, oleic and stearic acid). As palmitic acid is the major component with the use of both catalysts, but with different percentage concentrations. However, the enzymatic catalysis hydrolysis method was more feasible for the lipidic extraction of Scenedesmus ecornis, since the catalyst can be reused for up to two consecutive cycles, with the yield of ethyl fatty acid esters of 83% being changed in the first use to 78 % on second use. Thus, it is suggested that enzymatic catalysis via hydrolysis-esterification was the most viable method in the lipid extraction of the microalga Scenedesmus ecornis.

A síndrome de abstinência a Cannabis sativa resulta da inibição da interação da substância ∆⁹-tetrahidrocanabinol com receptores canabinoides do tipo1 (CB1). Objetivou-se propor candidatos a fármacos para esta síndrome utilizando-se métodos computacionais. Na database BindingDB selecionou-se moléculas agonistas do receptor CB1 das quais no webservidor Pharmagist derivou-se o grupamento farmacofórico utilizado no webservidor ZINCPharmer para a triagem de moléculas baseadas neste farmacóforo. A similaridade estrutural calculada no BindingDB teve o resultado analisado no software Discovery Studio onde as moléculas ZINC975899 (01), ZINC1730183 (02), ZINC2131499 (03), ZINC3850100 (04), ZINC3850106 (05), ZINC4023027 (06) e ZINC4023028 (07) apresentaram maior semelhança estrutural com a molécula Pivô CID104895 (A). As predições das propriedades farmacocinéticas e de toxicidade foram calculadas, respectivamente, nos programas QikProp e DEREK. Todas as moléculas apresentaram valores de 100% de absorção no trato Gastrointestinal; alta predição de permeabilidade aparente tanto para células Caco2, células MDCK e barreira hematoencefálica. Nenhuma apresentou violação a regra dos 5 de Lipinski, além de, não apresentarem alertas de toxicidade. A predição da atividade biológica realizada pelo site PASS indicou que todas as moléculas,com execeção da molécula 06, tiveram predição de atividade sobre estimulação sobre quinases ativadas por mitógenos e/ou inibição da adenilato ciclase. Somente a molécula 02, segundo o website SEA, demonstrou predição positiva ao receptor CB1 humano e camundongo, além de ser a única considerada de fácil acessibilidade química, de acordo com o software SYLVIA. Baseado nas predições apresentadas neste trabalho conclue-se que a molécula 02 demonstra ser uma favorável proposta a ser estudada para o desenvolvimento de um fármaco que pode ser utilizado na síndrome de abstinência de dependentes químicos de C. sativa, sendo indicado a continuidade desta pesquisa aplicando-se outros métodos computacionais e experimentais.