A novel series of ciprofloxacin hybrids comprising various heterocycle derivatives has been synthesized and structurally elucidated using 1H NMR, 13C NMR, and elementary analyses.
Using ciprofloxacin as a reference, compounds 1–21 were screened in vitro against Gram-positive
bacterial strains such as Staphylococcus aureus and Bacillus subtilis and Gram-negative strains such
as Escherichia coli and Pseudomonas aeruginosa. As a result, many of the compounds examined had
antibacterial activity equivalent to ciprofloxacin against test bacteria. Compounds 2–6, oxadiazole
derivatives, were found to have antibacterial activity that was 88 to 120% that of ciprofloxacin against
Gram-positive and Gram-negative bacteria. The findings showed that none of the compounds tested
had antifungal activity against Aspergillus flavus, but did have poor activity against Candida albicans,
ranging from 23% to 33% of fluconazole, with compound 3 being the most active (33% of fluconazole).
The most potent compounds, 3, 4, 5, and 6, displayed an IC50 of 86, 42, 92, and 180 nM against
E. coli DNA gyrase, respectively (novobiocin, IC50 = 170 nM). Compounds 4, 5, and 6 showed IC50
values (1.47, 6.80, and 8.92 M, respectively) against E. coli topo IV in comparison to novobiocin
(IC50 = 11 M).