Synthesis and In vitro Antibacterial Activity of N-[5-(5-nitroaryl)-1,3,4-Thiadiazol-2-yl] Piperazinyl Quinolones

Because resistance to antimicrobial drugs is widespread, recognition of new antimicrobial and understanding of their mechanisms are vital. The quinolones have a broad antibacterial spectrum of activity against Gram-positive, Gram-negative and mycobacterial pathogens such as anaerobes. In the present study, the synthesis and antibacterial activity of a new series of N-piperazinyl quinolones containing 5-(nitroaryl)-1, 3, 4-thiadiazole-2-yl moiety have been studied. In this laboratory study, the reaction of 1-cyclopropyl-6 fluoro-8 methoxy-4-oxo-7- (piperazin-1-yl)-1, 4- dihydroquinoline-3- carboxylic acid (compound 3), with 2-chloro-5-(nitroaryl)-1,3,4-thiadiazol (compounds 9a-f), in DMF in the presence of NaHCO3 at 85-90oC, gave final compounds 1- cyclopropyl- 6fluoro-7-[4-[5-(nitroaryl)-1,3, 4-thiadiazol-2yl], piperazin-1-yl] -8- methoxy-4-oxo-quinoline-3- carboxylic acid (8a-f). compounds 8a-f, were tested in vitro by the conventional agar dilution method against a panel of microorganisms including stophylococcus aureus, Escherichia coli, salmonella typhi, shigella flexneri, klebsiella pneumonia, serratia marcescens and pseudomonas aeruginosa. Among synthesized compound, nitrofuran analog 8b exhibited more potent inhibitory activity against Gram-positive bacteria including B. subtilis, S. epidermidis, E. feacalis, M. luteus, in respect to other synthesized compounds and reference drug gatifloxacin. Introduction of the bulky group of [5-(5-nitroaryl)-1,3,4-thiadiazol-2-yl] could dramatically impact the antibacterial activity of the parent quinolone, and among the nitroaryl groups, 5-nitrofuryl analogue showed the most potent antibacterial activity against the tested microorganisms.