Antiproliferative Activity of 8-methoxy Ciprofloxacin-Hydrozone/Acylhydrazone Scaffolds.

AIMS: A series of 8-methoxy ciprofloxacin- hydrazone/acylhydrazone hybrids were evaluated for their activity against a panel of cancer cell lines including HepG2 liver cancer cells, MCF-7, doxorubicin- resistant MCF-7 (MCF-7/DOX) breast cancer cells, DU-145 and multidrug-resistant DU145 (MDR DU-145) prostate cancer cells to seek for novel anticancer agents.

BACKGROUND

Ciprofloxacin with excellent pharmacokinetic properties as well as few side effects, is one of the most common used antibacterial agents. Notably, Ciprofloxacin could induce cancer cells apoptosis, and cell cycle arrest at the S/G2 stage. The structure-activity relationship reveals that the introduction of the methoxy group into the C-8 position of the fluoroquinolone moiety has resulted in a greater binding affinity to the binding site, and 8-methoxy ciprofloxacin derivatives have proved a variety of biological activities even against drug-resistant organisms. However, to the best of our current knowledge, there are no studies that have reported the anticancer activity of 8-methoxy ciprofloxacin derivatives so far. Furthermore, many fluoroquinolone-hydrazone/acylhydrazone hybrids possess promising anticancer activity. Thus, it is rational to screen the anticancer activity of 8-methoxy ciprofloxacin derivatives.

OBJECTIVE

To enrich the structure-activity relationship and provide new anticancer candidates for further investigations.

METHODS

The desired 8-methoxy ciprofloxacin-hydrazone/acylhydrazone hybrids 5 and 6 were screened for their in vitro anticancer activity against liver cancer cells HepG2, breast cancer cells MCF-7, MCF7/DOX, prostate cancer cells DU-145 and MDR DU-145 by MTT assay.

RESULTS

Some of 8-methoxy ciprofloxacin-hydrazone hybrids showed potential activity against HepG2, MCF-7, MCF-7/DOX, DU-145 and MDR DU-145 cancer cell lines, low cytotoxicity towards VERO cells and promising inhibitory activity on tubulin polymerization.

CONCLUSION

Compounds 5d and 5f showed promising anticancer activity, low cytotoxicity, and potential tubulin polymerization inhibitory activity, were worthy of investigation. Other: The structure-activity relationship was enriched.