Estudos por ancoramento e dinâmica molecular de potenciais inibidores da Nucleosídeo Hidrolase de Bacillus anthracis

Abstract

The enzyme nucleoside hydrolase (NH) is largely found in nature but not in mammals being, for this reason, seen as an ideal target to selective chemotherapy against parasitic diseases and bacterial infections like anthrax. Despite of availability of chemotherapy against anthrax today, the risk of resistance emergence is always present. Besides, it is likely that this drug be inefficient against genetically modified strains of Bacillus anthracis. So, considering the risk represented by anthrax today, as a chemical warfare agent, it is mandatory the search for new drugs against B. anthracis. In line with this, we performed in the present work, molecular docking studies in order to analyze the tridimensional positioning of 12 known inhibitors Tripanossoma vivax NH (TvNH) in the active site of B. anthracis NH (BaNH), as well as the main interactions of these compounds with aminoacids of the BaNH active site, and, also, to evaluate the relevant factors to the biological activity of such compounds. Further, we performed Molecular Dynamics (MD) simulations in order to check the docking results and select the most promising inhibitors as lead compounds to the design of potential inhibitors to BaNH. Docking results, besides corroborating with the MD simulations, suggested a good correlation with experimental results. We also observed that TvNH inhibitors could, as well, be excellent BaNH inhibitors.