Molecular Docking and Evaluation of Antileishmania Activity of a Ruthenium Complex with Epiisopiloturine and Nitric Oxide

Joabe Lima Araújo,Fernando Aécio De Amorim Carvalho,Gardênia Taveira Santos,Francisco Das Chagas Alves Lima,Kayo Alves Figueiredo,Ruan Sousa Bastos,Ionara Nayana Gomes Passos,Jefferson Almeida Rocha,Michel Muálem De Moraes Alves,Lucas Aires De Sousa

doi:10.4236/jbm.2020.85005

Abstract

Leishmaniasis is an infectious disease that affects both animals and humans, caused by flagellated parasites belonging to the genus Leishmania. The disease is estimated to reach about 700,000 to 1 million people, causing the deaths of 20 to 30,000 individuals annually. Thus, the present study aims to perform molecular docking tests and evaluation of antileishmania activity in vitro of a ruthenium complex with epiisopiloturine and nitric oxide. AutoDockTools-1.5.6 software was used to perform molecular docking tests. Molecular targets were considered rigid, and Epiruno2 considered flexible. The genetic algorithm Lamarckian (AGL) with global search and pseudo-Solis and Wets with local search were the methods adopted in the docking. The most promising results of molecular interaction were achieved in the targets Pteridine reductase and UDP-glucose Pyrophosphorylase with rates of -10.68 Kcal·mol-1 and -10.51 Kcal·mol-1, respectively. This demonstrates that Epiruno2 has molecular affinity with the targets of L. major. In vitro assays prove the antileishmania activity of the complex in the face of promastigote forms with inhibition of growth, concluding through this study that the Epiruno2 complex has antileishmania activity.

Highlights

Leishmaniasis is a disease that affects more than 98 countries worldwide, with about 700,000 to 1 million new cases reported annually, and an annual rate of 20 to 30,000 deaths [1]
The molecular docking between the Epiruno2 complex and the 1e7w protein obtained the lowest energy among all molecular couplings performed in this study, obtaining an energy of −10.68 Kcal∙mol−1 and an inhibition constant of 14.8 nM (Table 1)
The Epiruno2 complex showed 50.53% inhibition of promastigote growth at a concentration of 800 μg/mL (Figure 3), a significant reduction by analyzing the half maximal inhibitory concentration (CI-50) (Table 2) showing antileishmania activity, confirming the results presented in sílico tests by molecular docking

Summary

Introduction

Leishmaniasis is a disease that affects more than 98 countries worldwide, with about 700,000 to 1 million new cases reported annually, and an annual rate of 20 to 30,000 deaths [1]. The parasitic cycle results from the abundance of carbohydrates on the surface of Leishmania, which includes lipophosphoglycans, glycosylphosphatidylinositol lipid-anchored proteins and proteophosphoglycans [3] These glycoproteins are part of the promastigote infectious glycocalyx, which is the most important process in host infectivity [4] and phlebotomine interaction [5]. The patient undergoes treatment that depending on the infecting strain will be treated with some of the drugs available on the pharmaceutical market, they are: pentavalent antimonial; AmBisomew; liposomal; amphotericin B; miltefosine and diamidines, among others. All of these drugs are potentially toxic and have reduced efficacy in addition to adverse side effects. The patient chooses not to undergo treatment so that he does not suffer from side effects caused by drugs [6] [7]

Methods

Results

Conclusion