A holistic molecular modelling approach to design novel indole-2-carboxamide derivatives as potential inhibitors of MmpL3

• DOI: 10.1080/1062936x.2022.2096691
• Publication Date: 2022-07-19T07:44:45Z
• Authors: R. Ray; S. Das; M. Lobo; S.R. Birangal; G.G. Shenoy
• Keywords: Docking (animal); Molecular model; Molecular descriptor

Tuberculosis is an infectious air-borne disease and one of the leading causes death globally among all diseases. There urgent need to develop antitubercular drugs that would be highly efficient less toxic than presently available marketed drugs. Mycobacterium membrane protein large 3 (MmpL3) emerging drug target in tuberculosis with various classes molecules have been known inhibit it. In this study, a dataset indole-2-carboxamides showing activity by inhibiting MmpL3 was utilized. Initially, chimera-based homology model developed docking performed filtered analyse interactions. Thereafter, molecular dynamics simulations were run representative gain better insight on binding patterns. To attain more quantitative correlation, atom-based 3D QSAR which complemented results from previous models. A library novel then generated using core hopping-based ligand enumeration upon screening our workflow it predicted three as potent compounds. This work not only helps new insights interactions at site but also provides having potential become future.