Design, Synthesis and Molecular Docking of 1-Cyclopropyl-6- Fluoro-4-Oxo-7-{4-[2-(4-Substituted-Phenyl)-2-(Substituted)-Ethyl] -1-Piperazinyl}-1,4-Dihydroquinoline-3-Carboxylic Acid as an Antimicrobial Agents

Background: Quinolone scaffolds are widely used for the synthesis of a number of medicinal compounds with variety of biological activity. In view of the reported antimicrobial activity of various fluoroquinolones, the structure activity studies of various substituted quinolones, which proved the importance of the C-7 substituents to exhibit potent antimicrobial activities. Objective: Based on the structural activity relationship at C-7 position it was rationalized to design and synthesize new quinolone derivatives with increasing bulk at C-7 position of the main 6-fluoroquinolone scaffold. Methods: A novel series of 1-cyclopropyl-6-fluoro-4-oxo-7-{4-[2-(4-substituted-phenyl)- 2-(substituted)-ethyl]-1-piperazinyl}-1,4-dihydroquinoline-3-carboxylic acid derivatives were synthesized by reacting 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4- dihydroquinoline-3-carboxylic acid with 2-bromo-4-(substituted) acetophenone in the presence of sodium bicarbonate to obtain 1-cyclopropyl-6-fluoro-7-{4-[2-(4- substitutedphenyl)-2-oxoethyl]-1-piperazinyl}-4-oxo-1,4-dihydroquinoline-3-carboxylic acids 2a-2d. Compound 2a-2d underwent further reaction with different substituted hydrazide, hydroxylamine hydrochloride or methoxylamine in glacial acetic acid to give 3a-7d. In vitro antibacterial activity of the synthesized compounds 3a-7d was studied and the MIC value was determined by the broth dilution method. Result: Among all the synthesized compounds 3a-7d some compounds showed antimicrobial activity in comparison to the reference standard ciprofloxacin. Conclusion: The compound 6d showed the reasonable good antibacterial activity among all the tested compounds. To understand antibacterial data on structural basis and the interaction of binding sites with bacterial protein receptor, the docking studies were carried out using topoisomerase II DNA gyrase enzymes (PDB ID. 2XCT) by shrodinger's maestro program.