Molecular modeling of drug-pathophysiological Mtb protein targets: Synthesis of some 2-thioxo-1,3-thiazolidin-4-one derivatives as anti-tubercular agents

摘要

Twenty novel 2-thioxo-1, 3-thiazolidin-4-one derivatives (5a-5t) were synthesized and evaluated for their antitubercular activity. The structure of the compounds was confirmed by IR, NMR and Mass Spectroscopy methods. In addition, single-crystal X-ray diffraction was performed for compound 5a. All the synthesized compounds were screened for their in-vitro antimycobacterial activity against MTB (H37RV, ATCC No: 27294) by Alamar Blue assay method. Compounds 5r, 5k, 5t displayed most potent in-vitro activity with MICs of 0.05, 0.1, 0.2 mu g/ml concentrations respectively which are comparatively potent than the standards. Molecular docking and dynamics simulations were performed to find out the plausible mechanism of the titled compounds. (C) 2017 Elsevier B.V. All rights reserved.