New 1,2,3-triazole linked ciprofloxacin-chalcones induce DNA damage by inhibiting human topoisomerase I& II and tubulin polymerization.

A series of novel 1,2,3-triazole-linked ciprofloxacin-chalcones were synthesised as potential anticancer agents. Hybrids exhibited remarkable anti-proliferative activity against colon cancer cells. Compounds displayed ICs ranged from 2.53-8.67 µM, 8.67-62.47 µM, and 4.19-24.37 µM for HCT116, HT29, and Caco-2 cells; respectively, whereas the doxorubicin, showed IC values of 1.22, 0.88, and 4.15 µM. Compounds and were the most potent against HCT116 with IC values of 3.57, 4.81, 4.32, 4.87, and 2.53 µM, respectively, compared to doxorubicin (IC = 1.22 µM). Also, hybrids and exhibited remarkable inhibitory activities against topoisomerase I, II, and tubulin polymerisation. They increased the protein expression level of γH2AX, indicating DNA damage, and arrested HCT116 in G2/M phase, possibly through the ATR/CHK1/Cdc25C pathway. Thus, the novel ciprofloxacin hybrids could be exploited as potential leads for further investigation as novel anticancer medicines to fight colorectal carcinoma.