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A Leishmaniose é uma doença infecciosa que ocasiona a morte de 26.000 a 65.000 pessoas anualmente, estima-se que no ano de 2019 houve 700.000 a 1 milhão de novos casos. Estes dados são preocupantes e está relacionado à falta de saneamento básico que favorece a proliferação dos vetores, além da ausência de medicamentos eficientes com mecanismos de ação alternativos e com menos efeitos colaterais. Em meio a essa necessidade de novos agentes inibitórios, este estudo teve como objetivo realizar uma predição computacional de alvos moleculares de Leishmania para um complexo metálico de rutênio com epiisopiloturina e óxido nítrico (Epiruno2). O processo de docking molecular foi realizado empregando-se o software Autodock Tools (ADT) versão 1.5.6. As proteínas alvos foram consideradas rígidas, enquanto que o Epiruno2 foi considerado flexível. A glicoproteína GP63 (1lml) representa mais de 1% da proteína total do parasito tendo em vista que a 1lml é uma metaloprotease que predomina grupos funcionais em seu sítio ativo, torna-se um alvo atrativo em estudos de atividade inibitória. O docking molecular entre o Epiruno2 e a 1lml resultou na melhor conformação de encaixe deste estudo, com energia de Gbind a de -8,05 Kcal.mol-1 e uma constante de inibição de 1,26 µM. Também foi observada a formação de quatro pontes de hidrogênio, demonstrando ser um forte candidato a fármaco antileishmania. Concluindo-se que o composto Epiruno2 é clinicamente atrativo para estudos experimentais futuros ex vivo, in vitro e in vivo, pois seus resultados in sílico apresentaram boas interações moleculares para todas as proteínas alvo deste estudo. Leishmaniasis is an infectious disease that causes the death of 26,000 to 65,000 people annually, it is estimated that in 2019 there were 700,000 to 1 million new cases. These data are worrying and are related to the lack of basic sanitation that favors the proliferation of vectors, in addition to the absence of efficient drugs with alternative mechanisms of action and with less side effects. Amid this need for new inhibitory agents, this study aimed to perform a computational prediction of Leishmania molecular targets for a ruthenium metal complex with epiisopiloturine and nitric oxide (Epiruno2). The molecular docking process was performed using the Autodock Tools (ADT) software version 1.5.6. The target proteins were considered rigid, while Epiruno2 was considered flexible. The glycoprotein GP63 (1lml) represents more than 1% of the total protein of the parasite, considering that 1lml is a metalloprotease that predominates functional groups in its active site, it becomes an attractive target in studies of inhibitory activity. The molecular docking between Epiruno2 and 1lml resulted in the best fit conformation in this study, with Gbinda energy of -8.05 Kcal.mol-1 and an inhibition constant of 1.26 µM. The formation of four hydrogen bonds was also observed, demonstrating to be a strong candidate for antileishmania drug. In conclusion, the compound Epiruno2 is clinically attractive for future experimental studies ex vivo, in vitro and in vivo, as in silico results showed good molecular interactions for all the target proteins in this study.

A series of drugs was investigated to determine structural, electronic and pharmacological properties, as well as the molecular affinity for the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The drugs were submitted to density functional theory calculations to optimize structures and predict binding preferences. The optimized geometries were used in molecular docking simulations. In the docking study, the receiver was considered rigid and the drugs flexible. The Lamarckian genetic algorithm with global search and Pseudo-Solis and Wets with local search were adopted for docking. Absorption, distribution, metabolism, excretion and toxicological properties were obtained from the Pre-ADMET online server. In this series, the antiviral atazanavir showed the potential to inhibit the main protease of SARS-CoV-2, based on the free binding energy, inhibition constant, binding interactions and its favorable pharmacological properties. Therefore, we recommend carrying out further studies with in vitro tests and subsequent clinical tests to analyze its effectiveness in the treatment of SARS-CoV-2. © 2021 Sociedade Brasileira de Quimica.

Objective : The objective of this work is to perform a bioactive analysis of Leishmania major Pteridine Reductase 1 inhibitors (LmPTR1) through in silico molecular docking studies. Method : The receptor and the ligands were prepared using CHIMERA v. 13.1 suppressing all waste. The Lamarckian Genetic Algorithm (LGA) with global search and pseudo-Solis and Wets with local search, were the methods used in molecular docking. Each simulation consisted of 100 independent runs. The rest of the parameters were set to default values. Results : The main molecular interaction between the ligand and the receptor obtained -7.05 kcal.mol -1 of binding energy for the paromomycin, however the highest inhibition constant was obtained between the simulation of miltefosine with the receptor, obtaining 58.21 μM of inhibition constant. Conclusion : The results reveal a reduced efficacy of the four drugs tested in this