in silico Quest Guided by Physico-Chemical Descriptors of Bedaquiline for New Scaffolds with Potential Inhibitory Capacity against Homology Model of Mycobacterium F1F0 ATP Synthase

Abstract

As the first US FDA approved drug for treating pulmonary multi drug resistant tuberculosis (MDR-TB) in the last 40 years, bedaquiline (TMC207, Sirturo TM ) stands out as cynosure in the circles of synthetic chemists exploring new therapeutics against tuberculosis. The remarkable efficacy of bedaquiline in treating tuberuculosis lies in its ability to target the energy metabolism that affects both replicating as well as dormant forms of M. tuberculosis (MTB). Despite its promising antitubercular profile, bedaquiline raises serious concern with its string of side effects and emergence of resistant strains, warrants a quest for better substitutes. In the present work, we employed in silico methods like homology modeling and virtual screening to zero in on molecules that exhibit high affinity at the binding site of bedaquiline.