Estudos in silico de potenciais inibidores da enzima di-hidrifolato redutase de Bacillus anthracis e de uma oxima reativadora da acetilcolinesterase

Abstract

Chemical and biological weapons are classified as weapons of mass destruction, because when used has the ability to cause large numbers of deaths. The low cost, ease of manufacturing, advances in biotechnology and the ease of hiding production facilities of chemical and biological weapons makes them increasingly attractive to terrorist groups. Currently it is clear that no country in the world is in ideal conditions to meet an attack with such weapons. Thus, besides the military preparation is essential to the search for new drugs and new molecular targets for the development of new antidotes and/or drugs against biological and chemical weapons. This study was conducted in two stages: first a study on the chemical warfare in which we analyzed the reactivation by oxime BI-6 enzyme acetylcholinesterase inhibited by different organophosphorus. To this was applied a theoretical methodology docking and QM/MM using the software Spartan® and Molegro®. The second part refers to biological warfare and consisted of assessing the selectivity of inhibitors of the enzyme dihydrofolate reductase from Bacillus anthracis (BaDHFR), and correlation between experimental and theoretical results and propose a new framework that can provide better inhibitory ability. For this step, and docking studies were performed molecular dynamics calculations using the program GROMACS. Importantly, the use of computational chemistry techniques in the study of issues related to chemical and biological warfare is especially useful as a way to reduce the need for handling these substances in the laboratory, saving reagents and materials investments and gain time the search for new drugs and antidotes.