In-silico Studies, Synthesis, and Antibacterial Evaluation of Thiophene Linked Isoxazole Derivatives

In this work a series of thiophene linked isoxazole derivatives (LK1-LK8) was synthesized by cyclization of different substituted thienyl chalcones (PL1-PL8). The structures of the synthesized compounds were characterized by IR, H-1 NMR and mass spectral data. These derivatives were evaluated for antibacterial activities. Compounds LK7 showed excellent antibacterial activities amongst the synthesized compounds with MIC value 6.75 mu g/ml. Molecular docking of these linked isoxazole derivatives (LK1-LK8) was also performed with crystal structure of staph gyrase B 24kDa (PDB code: 5 4URM). All the isoxazole derivatives (LK1-LK8) were docked into same groove of the binding site of native co-crystallized (1R,4aS,5S,6S,8aR)-5-{[(5S)-1-(3-O-acetyl-4-O-carbamoyl-6-deoxy-2-O-methyl-alpha-L-talopyra nosy 1)-4 hydroxy 2-oxo-5-(propan-2-yl)-2,5-dihydro-1H-pyrrol-3-yl]carbonyl}-6-methyl-4 1, 2, 3, 4 methylid-ene, 4a,5,6,8a-octahydronaphthalen-1-yl2,6-dideoxy-3- C-[(1S)-1-{[(3,4-dichloro-5-methyl-1 H-pyrrol-2-yl) carbonyl]amino}ethyl]-beta-D-ribohexopyranoside) ligand for activity explanation and exhibited good ligand interaction and binding affinity were of range -2.04 to -4.34 kcal/mol.