AN IN SILICO STUDY OF NOVEL FLUOROQUINOLONES AS INHIBITORS OF DNA GYRASE OF STAPHYLOCOCCUS AUREUS
Keywords:
S aureus, (FQ)s, 2XCT, DNA gyrase, Nil, iGemdock, In silicoAbstract
Objective: This study is an attempt to identifying an effective fluoroquinolones (FQ) s against STAPHYLOCOCCUS AUREUS (S. aureus) by in silico analysis of 150 (FQ) compounds using iGemDock v2.1 tool.
Methods: Structure of DNA gyrase (2XCT) was retrieved from the Protein Data Bank (PDB) and the structures of (FQ) compounds were selected from literature survey of 400 novel compounds and the physical, chemical and molecular characteristics of each compound were obeyed for drug-relevant properties based on Lipinski's rule of five, then a total of 150 (FQ)s were docked against the protein of the 2XCT enzyme.
Results: From this study, it was found that the compound (1) [(3R,7E)-9-fluoro-7-(isonicotinoylhydrazono)-3-methyl-10-(4-methylpiperazin-1-yl)-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid] and the compound (2) [1-cyclopropyl-6-fluoro-7-{4-[(8-hydroxyquinolin-2-yl)methyl]piperazin-1-yl}-4-oxo-1,4-dihydroquinoline-3-carboxylic acid] showed the best interaction value against 2XCT enzyme, the binding energy was (-104. 58 kcal/mol), (-26. 5kcal/mol) respectively whereas the reference ciprofloxacin (CIP) was (-74. 33 kcal/mol).
Conclusion: Further in vitro studies of these compounds against the enzyme will lead a new pathway to drug discovery.
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