A series of novel thiazole-based chalcones were evaluated for their anticancer activity as potential tubulin polymerization inhibitors. In vitro anticancer screening for the thiazole derivatives 2a–2p exhibited broad-spectrum antitumor activity against various cancer cell lines particularly Ovar-3 and MDA-MB-468 cells with a GI₅₀ range from 1.55 to 2.95 μΜ, respectively. Compound 2e demonstrated significant inhibition of tubulin polymerization, with an IC₅₀ value of 7.78 μM compared to Combretastatin-A4 (CA-4), with an IC₅₀ value of 4.93 μM. Molecular docking studies of compounds 2e, 2g, and 2h into tubulin further supported these findings, revealing that they bind effectively to the colchicine binding site, mirroring key interactions exhibited by CA-4. Computational predictions suggested favorable oral bioavailability and drug-likeness for these compounds, highlighting their potential for further development as chemotherapeutic agents.

A novel series of thiazole chalcone/ciprofloxacin hybrids were synthesized and screened for their anticancer activity against NCI-60 cancer cell lines, USA. Interestingly, compounds 4b and 4d exhibited potent antiproliferative activities, particularly against leukemia HL-60, RPMI-8226, and colon HCT-116 cells, with IC₅₀ values of 0.3–3.70 µM. Importantly, compounds 4b and 4d exhibited enhanced selectivity for cancer cells relative to doxorubicin with IC₅₀ values of 26.80, 41.20, and 19.80 µM, respectively. Mechanistic investigations revealed that compounds 4b and 4d inhibited topoisomerases (Topo) I/IIβ activity, being fourfold and twofold more effective than untreated controls, respectively. Furthermore, these compounds induced G1 phase cell cycle arrest and promoted apoptosis, which likely explain their potent anticancer properties. In depth, compound 4d increased the relative gene expression of pro-apoptotic Bax (5.58-fold) and caspase-3 (10.86-fold) as well as the initiator caspase-9 (4.2-fold), and reduced the relative gene expression of Bcl-2. Therefore, ciprofloxacin/thiazole chalcone derivatives, particularly 4b and 4d, may serve as promising candidates for the development of antitumor agents.