Identification of N-Benzylated Indole Mannich Bases as Potential Anti TB Agents by Using Computational Studies and Molecular Hybridization Technique

摘要

Introduction: Morbidity and mortality due to tuberculosis are rising steadily. Despite havingefficient drugs and treatment protocols, microbial drug resistance often leads to treatment failure. Effortsto bring novel drugs to combat this menace are hampered by several issues including problems ingaining industry support, motivation and ethical issues clinical trials. Bedaquiline and Delaminid arethe only novel drugs approved in the last three decades for treating TB. A few more molecules anddrug combinations are still in clinical trials. One such drug is the BM212, a potent anti-TB agent whichacts by a novel mechanism of action.Methods: In the present study, we used virtual screening method with a combination of molecular hybridizationtechnique to design N-benzylated Indole Mannich bases as potent anti-TB agent based onBM212 pharmacophore. The library of designed molecules was prepared and screened using BM212model. The top 5 ‘hit’ molecules were selected (with good TC score >1.15), synthesized and screenedfor anti TB activity by MABA assay method.Results and Conclusion: All the compounds showed excellent anti TB activity, of which 4 compoundshave shown MIC ≤12.5 μg/mL. Our protocol could help in the designing of newer anti-TB agents withbetter bioactivity profile.