Synthesis, Characterization and Docking Studies of N-Methyl-2, 3-Dihydro Quinazolin-4-Ones Linked 1,3-Thiazole Hybrids as Potent Anti-Tubercular Agents

Quinazolin-4-ones connected 1, 3-thiazole were found with antibacterial action after high throughput screening. N-Methyl Anthranilic acid when treated with thiophene-2-carboxylic acid gives 1-Methyl-2(thiophen-2-yl)-1,2-dihydro-4H-3,1-Benzoxazin-4-one which on further treatment with 4-substituted phenyl-1,3-thiazol-2-amines gives 1-Methyl-3-(4-Substituted phenyl-1,3-thiazol-2yl)-2-(thiophen-2-yl)-2,3-dihydro quinazoline-4(1H)-ones (5Fa1-5Fk11) were obtained. The structural identification was done through Infra-red, H-1- Nuclear magnetic resonance, C-13- Nuclear magnetic resonance, and Mass spectrometry. These derivatives were screened for anti-tubercular activity against Mycobacterium tuberculosis H37RV using the micro plate alamar blue assay method. Compounds 5Ff6, 5Fe5, 5Fb2, and 5Fd4 displayed better antibacterial activity at minimum inhibitory concentration 12.5 and 6.25 mu g/ml. Further, 5Ff6 displayed a favourable inhibition at minimum inhibitory concentration 6.25 mu g/ml, contrasted with the reference drug Isoniazide. The compounds were docked where they exhibited associations with both the vital site of penicillin-binding protein 2a and Mycobacterium tuberculosis H37Rv organism. All the derivatives showed good affinity towards the protein when compare with the standard drug. Here 5Ff6 was observed to interact with three amino acids, viz., Agn104, Lys273, and Tyr297, as signified by the great interaction energy (Delta G=-4.2 kcal/mol).