Design, synthesis and docking studies of quinoline-oxazolidinone hybrid molecules and their antitubercular properties
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2011
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Abstract
New series of quinoline-oxazolidinone hybrid molecules were synthesized based on the preliminary docking studies. All the newly synthesized compounds were characterized by spectral analyses. The newly synthesized compounds were screened for their antimycobacterial properties based on the promising preliminary antibacterial screening results. Amongst tested compounds, compounds 8a, 8j and 13a were active at 0.65 ?g/mL against Mycobacterium tuberculosis H <inf>37</inf>Rv strain. The mode of action of these active compounds was carried out by docking of receptor enoyl-ACP reductase with newly synthesized candidate ligands 8a, 8j and 13a. These compounds exhibited well established bonds with one or more amino acids in the receptor active pocket. From the docking studies, compound 8j was considered to be the best inhibitor. © 2011 Elsevier Masson SAS. All rights reserved.
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2 (5 cyclopentylaminomethyl 2 oxo oxazolidin 3 yl) n (6 methoxy 2 methyl quinolin 4 yl)acetamide, 2 (5 cyclopropylaminomethyl 2 oxo oxazolidin 3 yl) n (6 methoxy 2 methyl quinolin 4 yl)acetamide, 2 (5 diethylaminomethyl 2 oxo oxazolidin 3 yl) n (6 methoxy 2 methyl quinolin 4 yl)acetamide, 2 (5 dimethylaminomethyl 2 oxo oxazolidin 3 yl) n (6 methoxy 2 methyl quinolin 4 yl)acetamide, 2 [5 ((4 acetyl piperazin 1 yl)methyl) 2 oxo oxazolidin 3 yl] n (6 methoxy 2 methyl quinolin 4 yl)acetamide, 2 [5 ((4 ethyl piperazin 1 yl)methyl) 2 oxo oxazolidin 3 yl] n (6 methoxy 2 methyl quinolin 4 yl)acetamide, 2 [5 ((4 isopropyl piperazin 1 yl)methyl) 2 oxo oxazolidin 3 yl] n (6 methoxy 2 methyl quinolin 4 yl)acetamide, 2 [5 ((4 tert butyl piperazin 1 yl)methyl) 2 oxo oxazolidin 3 yl] n (6 methoxy 2 methyl quinolin 4 yl)acetamide, 2 [5 ((cyclohexyl methyl amino)methyl) 2 oxooxazolidin 3 yl] n (6 methoxy 2 methyl quinolin 4 yl)acetamide, 2 fluoro n [3 (6 methoxy 2 methyl quinolin 4 yl) 2 oxo oxazolidin 5 ylmethyl]benzamide, 4 chloro n [3 (6 methoxy 2 methyl quinolin 4 yl) 2 oxo oxazolidin 5 ylmethyl]benzamide, 4 ethyl n [3 (6 methoxy 2 methyl quinolin 4 yl) 2 oxo oxazolidin 5 ylmethyl]benzamide, 4 fluoro n [3 (6 methoxy 2 methyl quinolin 4 yl) 2 oxo oxazolidin 5 ylmethyl]benzamide, 4 methoxy n [3 (6 methoxy 2 methyl quinolin 4 yl) 2 oxo oxazolidin 5 ylmethyl] 2 methylbenzamide, 4 methoxy n [3 (6 methoxy 2 methyl quinolin 4 yl) 2 oxo oxazolidin 5 ylmethyl]benzamide, n (6 methoxy 2 methyl quinolin 4 yl) 2 (2 oxo 5 piperidin 1 ylmethyl oxazolidin 3 yl)acetamide, n (6 methoxy 2 methyl quinolin 4 yl) 2 (2 oxo 5 pyrrolidin 1 ylmethyl oxazolidin 3 yl)acetamide, n (6 methoxy 2 methyl quinolin 4 yl) 2 (5 morpholin 4 ylmethyl 2 oxo oxazolidin 3 yl)acetamide, n (6 methoxy 2 methyl quinolin 4 yl) 2 [5 ((4 methylpiperazin 1 yl)methyl) 2 oxo oxazolidin 3 yl]acetamide, n (6 methoxy 2 methyl quinolin 4 yl) 2 [5 (4 methylpiperidin 1 ylmethyl) 2 oxo oxazolidin 3 yl]acetamide, n [(3 (6 methoxy 2 methylquinolin 4 yl) 2 oxo 1,3 oxazolidin 5 yl)methyl]acetamide, n [(3 (6 methoxy 2 methylquinolin 4 yl) 2 oxo 1,3 oxazolidin 5 yl)methyl]cyclobutane carboxamide, n [(3 (6 methoxy 2 methylquinolin 4 yl) 2 oxo 1,3 oxazolidin 5 yl)methyl]cyclopropane carboxamide, n [3 (6 methoxy 2 methyl quinolin 4 yl) 2 oxo oxazolidin 5 ylmethyl] 4 methylbenzamide, n [3 (6 methoxy 2 methyl quinolin 4 yl) 2 oxo oxazolidin 5 ylmethyl] 4 trifluoromethylbenzamide, n [3 (6 methoxy 2 methyl quinolin 4 yl) 2 oxo oxazolidin 5 ylmethyl]benzamide, oxazolidinone derivative, quinoline derivative, tuberculostatic agent, unclassified drug, unindexed drug, antibacterial activity, article, bacterial strain, controlled study, drug design, drug receptor binding, drug screening, drug synthesis, Escherichia coli, Klebsiella pneumoniae, molecular docking, Mycobacterium fortuitum, Mycobacterium smegmatis, Mycobacterium tuberculosis, nonhuman, Pseudomonas aeruginosa, spectroscopy, Staphylococcus aureus, Streptococcus pyogenes, Anti-Bacterial Agents, Antitubercular Agents, Bacteria, Catalytic Domain, Drug Design, Enoyl-(Acyl-Carrier-Protein) Reductase (NADH), Humans, Models, Molecular, Oxazolidinones, Protein Binding, Quinolines, Tuberculosis
Citation
European Journal of Medicinal Chemistry, 2011, 46, 10, pp. 4834-4845