Synthesis and anti-tumor activity of ciprofloxacin-histone deacetylase inhibitor conjugates / 药学学报

ABSTRACT

Eighteen novel ciprofloxacin-histone deacetylase inhibitor (HDACi) conjugates were designed and synthesized from suberic acid and ciprofloxacin via esterification and amidation reaction. All conjugates were confirmed by the application of 1H NMR and HR-MS spectra, their activities against HDACs were evaluated by HDACs assay kit and the anti-tumor activities were evaluated in five cancer cells with CCK-8 assay. The preliminary biological results showed that these conjugates displayed potent activity against HDACs and significant anti-proliferative effect on the cancer cells. Some conjugates exhibited activities better than that of the parent compound ciprofloxacin and drug SAHA. Specifically, compound 12b exhibited the most potent anti-HDAC1 (IC50=0.041±0.005 μmol·L-1) and HDAC6 (IC50=0.039±0.006 μmol·L-1) activities, and also showed the greatest potency against NCI-H460 (IC50=0.7±0.04 μmol·L-1) and A549 (IC50=0.9±0.12 μmol·L-1). These results suggest that the histone deacetylase inhibitors have significant anti-tumor activities, which can enhance the anti-tumor activity of quinolones.