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 IC₅₀s 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 IC₅₀ values of 1.22, 0.88, and 4.15 µM. Compounds 4a, 4b, 4e, 4i, and 4j were the most potent against HCT116 with IC₅₀ values of 3.57, 4.81, 4.32, 4.87, and 2.53 µM, respectively, compared to doxorubicin (IC₅₀ = 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. Graphical Abstract

Fluoroquinolones represent an interesting synthetic class of antimicrobial agents with broad spectrum and potent activity. Since the discovery of nalidixic acid, the prototype of quinolones, several structural modifications to the quinolone nucleus have been carried out for improvement of potency, spectrum of activity, and to understand their structure activity relationship (SAR). The C-7 substituent was reported to have a major impact on the activity. Accordingly, Substitution at C-7 or its N-4-piperazinyl moiety was found to affect potency, bioavailability, and physicochemical properties. Also, it can increase the affinity towards mammalian topoisomerases that may shift quinolones from antibacterial to anticancer candidates. Moreover, the presence of DNA topoisomerases in both eukaryotic and prokaryotic cells makes them excellent targets for chemotherapeutic intervention in antibacterial and anticancer therapies. Based on this concept, several fluoroquionolones derivatives have been synthesized and biologically evaluated as antibacterial, antituberculosis, antiproliferative, antiviral and antifungal agents. This review is an attempt to focus on the therapeutic prospects of fluoroquinolones with an updated account on their atypical applications such as antitubercular and anticancer activities.