Synthesis, Anticancer Evaluation, and In Silico Modeling Study of Some N-Acylated Ciprofloxacin Derivatives

Fluoroquinolones constitute a well-known class of antibacterial agents that also display significant anticancer activity. In recent years, various antibacterial fluoroquinolones have been effectively converted to antitumor fluoroquinolones. To further explore potent antitumor fluoroquinolones, a variety of novel N-acylated ciprofloxacin scaffolds were obtained by reacting a variety of carboxylic acids or acyl and sulfonyl halides with ciprofloxacin methyl ester and were characterized by IR and H-1 and C-13 NMR spectroscopic techniques. The cytotoxic activity of the synthesized derivatives was checked against MCF-7 tumor cell line, and some com-pounds showed a notable anticancer effect. In silico modeling of methyl 7-[4-(2-bromoacetyl)piperazin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate (3a, IC50 2.0 mu g/mL) further highlighted the mechanistic insights of its anticancer potential. The topoisomerase II inhibition was investigated by induced fit docking, and the results revealed that this compound inhibits topoisomerase II with higher affinity and seems to be a promising lead compound in future to develop potent anticancer agents.