A series of novel 1,2,3-triazole-linked ciprofloxacin-chalcones
4a-j
were synthesised as potential anticancer agents. Hybrids
4a-j
exhibited remarkable anti-proliferative activity against colon cancer cells. Compounds
4a-j
displayed IC
50
s 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
50
values of 1.22, 0.88, and 4.15 µM. Compounds
4a, 4b, 4e, 4i,
and
4j
were the most potent against HCT116 with IC
50
values of 3.57, 4.81, 4.32, 4.87, and 2.53 µM, respectively, compared to doxorubicin (IC
50
= 1.22 µM). Also, hybrids
4a, 4b, 4e, 4i,
and
4j
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.