Molecular docking studies in multitarget antitubercular drug discovery

Abstract

Tuberculosis, caused by Mycobacterium tuberculosis, is an infectious disease with high levels of mortality worldwide, currently with approximately 6.3 million new cases per year that often present resistance to both first- and second-line drugs. These high rates of incidence are due to several factors including bacterial resistance, AIDS cases, and latent tuberculosis that can reoccur in the patient. Among methods used in the search for new tuberculosis drugs are in silico or CADD (computer-aided drug design) studies, which are increasingly being employed in industry and universities. They investigate molecular interactions in order to understand both the structural characteristics of compounds and their activities through virtual manipulation of their three-dimensional (3D) molecular structures, as is the case with molecular docking. Such analyses allow extraction of information and characteristics relevant to compound activity, as well as to predict potential application. In our studies, we discovered antituberculotic activity in various derivatives: thiophenes, sulfonamides, chalcones, nitroimidazoles, benzimidazoles, peptides, and quinolones with action in several specific M. tuberculosis enzymes. For each derivative, multitarget activity was evaluated in molecular docking studies to select promising compounds with activity(s) against tuberculosis. This chapter will present and discuss molecular docking studies within the bacillus complex, the pharmacological potential of multitarget compounds, and new promising drug candidates with high levels of specificity.