Molecular docking studies of benzothiazinone derivatives in the search for new tuberculostatic agents

Abstract

Despite the efforts to reduce the rate of infection, the resurgence of Tuberculosis, accompanied by strains of Mycobacterium tuberculosis, calls attention to the search for new drugs that can bypass resistance mechanisms. Among the strategies for the development of antitubercular lead compounds, benzothiazinones (BTZ) are included, with highly selective mechanism of action of DprE1 flavoenzyme. We studied four compounds in the antituberculosis activity (IC 50 values between 0.029 -0.060 μg/ml). These derivatives were subjected to energy minimization and Molecular Docking calculations in the software Molegro Virtual Docker, from which the binding free energy calculations showed that the suggested compounds had better binding affinity with DprE1 when compared to PBTZ169, a crystallized inhibitor of DprE1. Our results showed that the compounds showed similar crucial binding interactions between the compounds, which may determine that there was molecular rearrangement within the active site itself. Thus, our studies evidenced the probable interactions that favor the activity of the derivatives, as well as other interactions of the compounds with other residues not reported in the literature, and these may act as lead compounds in the development of new antituberculosis drugs.