Background and purpose: In recent years, the incidence of cancers has increased in the world. Therefore, many researches have focused on new strategies for treatment of cancers. Previous studies showed that quinolone antibacterials can inhibit human topoisomerases at high concentrations and can be considered as potential cytotoxic agents. On the other hand, 5,7-dibromoisatin is a cytotoxic agent and inhibits tubulin polymerization. Accordingly, a series of ciprofloxacin-isatin conjugates were prepared as potential cytotoxic agents.

Materials and methods: Isatin was dibrominated by bromine in refluxing ethanol. The 5,7-dibromoisatin was reacted with ciprofloxacin in the presence of paraformaldehyde to produce N-Mannich base of ciprofloxacin. Furthermore, 5,7-dibromoisatin was reacted with 1-bromo-2-chloroethane to give N-(2-chloroethyl)-5,7-dibromoisatin. The latter compound was reacted with ciprofloxacin to afford related conjugate analog containing two carbons linker. All compounds were purified by extraction and crystallization. The structures of compounds were assigned by IR and NMR spectroscopy.

Results: Conveniently, several new conjugates of ciprofloxacin and isatin containing methylene or ethylene linker were prepared. The isolated yields for final compounds were 23 to 34%. In the preparation of final compounds with methylene linker (compounds 4a and 4b), ethanol was found to be the best solvent while N,N-dimethylformamide (DMF) was an appropriate solvent for preparation of compound 4c, bearing an ethylene linker. The final products were re-crystallized from DMF or DMF-water.

Conclusion: The conjugate analogs of ciprofloxacin and isatin derivatives can be obtained using an appropriate and convenient method. The designed compounds have both pharmacophoric motifs of quinolones and isatin and potentially can be considered as new cytotoxic agents.