QSAR, Pharmacophore and Molecular Docking Studies for the Design of Novel Arylamide-derived Inhibitors of Mycobacterium tuberculosis

Abstract

Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosis. It remains a significant public health challenge worldwide. In 2022, approximately 10.6 million people were diagnosed with tuberculosis, and 1.3 million individuals lost their lives to the disease. This manuscript presents our research focused on designing new inhibitors for the enoyl acyl carrier protein reductase (InhA) of Mycobacterium tuberculosis. This enzyme is vital as it plays a key role in the type II fatty acid biosynthesis pathway of M. tuberculosis. To conduct our study, we utilized computer simulations, specifically docking and quantitative structure-activity relationship (QSAR) analysis on free molecules. We applied these methods to a series of arylamide-derived inhibitors, the efficacy of which was proposed by He et al. The results obtained from our docking and QSAR analyses confirm the robustness of the molecules identified by He et al., based on their experimental activities. Furthermore, the docking results facilitated the generation of a pharmacophore model, which was instrumental in designing a new inhibitor of Mycobacterium tuberculosis InhA. This new compound demonstrates enhanced activity compared to previously identified inhibitors. Such advancements could significantly contribute to the development of novel treatments for tuberculosis and help address this critical global health issue.