In-silico Studies, Synthesis, and Antibacterial Evaluation of Thiophene Linked Isoxazole Derivatives
Lenisha Crasta
Department of Pharmaceutical Chemistry, Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Deralakatte, Mangaluru-575018, India.
K. H. Khadeejath Suhana
Department of Pharmaceutical Chemistry, Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Deralakatte, Mangaluru-575018, India.
Khatheeja Afrana
Department of Pharmaceutical Chemistry, Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Deralakatte, Mangaluru-575018, India.
. Kshema
Department of Pharmaceutical Chemistry, Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Deralakatte, Mangaluru-575018, India.
Pankaj Kumar *
Department of Pharmaceutical Chemistry, Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Deralakatte, Mangaluru-575018, India.
*Author to whom correspondence should be addressed.
Abstract
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, 1H 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 µg/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 l)-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-ribo-hexopyranoside) ligand for activity explanation and exhibited good ligand interaction and binding affinity were of range -2.04 to -4.34 kcal/mol.
Keywords: Isoxazole, thiophene, docking, antibacterial activity