Design, synthesis, antimycobacterial activity and molecular docking studies of novel 3- (N-substituted glycinamido) benzoic acid analogues as anti tubercular agents

[Display omitted] •Novel derivatives of 3-(N-substituted glycinamido) benzoic acid have been synthesised using various aliphatic and aromatic amines.•The synthesised compounds exhibited potent antimycobacterial activity carried out using MABA assay.•Molecular docking studies revealed important binding interactions of the compounds within the active site of the MmaA1 protein.•In silico ADMET studies aided in identifying promisable lead compounds. We have recently identified mycolic acid methyl transferase (MmaA1) enzyme inhibitors as potential antitubercular agents using in silico modelling techniques. In continuation of that study, we synthesised a series of novel 3-(N-substituted glycinamido) benzoic acid derivatives with an aim to optimise the lead molecule. The newly synthesised compounds were evaluated for their in vitro antimycobacterial activity against M. tuberculosis H37Rv. Among these, 5 compounds A3, A4, A5, A6 and A10 exhibited most potent activity with an MIC value of 1.6 μg/ml. Further molecular docking studies were carried out to investigate the binding mode of the ligands with MmaA1 protein. The docking studies revealed that the ligands made strong interactions with the catalytic site residues TRP30, TYR 32, GLY 71, TRP 74, GLY 76, ALA 77 and GLU 136 of MmaA1 protein. Druglikeness and leadlikeness properties of the compounds were also studied using computational tools. The results of in silico and in vitro studies indicate that these novel compounds are propitious leads for tuberculosis therapy.