Unveiling the potential of zingerone-1,2,3-triazole derivatives as dual anticancer and COX-2 inhibitor: design, synthesis, and biological assessments.

AIM: Cyclooxygenase-2 (COX-2) is reported to be upregulated in many cancers that promote cancer growth and angiogenesis. Therefore, inhibiting COX-2 can inhibit cancer growth and advances its treatment. In the present work, Zingerone, a reported anticancer agent, has been hybridized with 1,2,3-triazole scaffold to develop effective anticancer compounds targeting COX-2 enzyme.

MATERIALS AND

METHODS

Eleven zingerone-1,2,3-triazole hybrids (3-13) have been synthesized and assessed for antiproliferative activity against HepG2, MCF-7, and HCT-116 cell lines and COX-2 inhibition. Cell cycle and apoptosis studies have also been carried out for the best candidate by flow cytometry. Molecular docking and ADMET profiles were performed to inquire about drug likeness parameters.

RESULTS AND DISCUSSION: Among all the zingerone hybrids, compound 11 was found to be the most promising cytotoxic agent with IC50 1.86 against HepG2 and displayed COX-2 inhibitory effect with IC50 0.21 µM. The same compound also arrests cell cycle at G2/M phase and triggers late apoptosis with 95.33% in HepG2 cells. The docking study revealed strong hydrophobic interactions with key residues of the COX-2 protein. Furthermore, zingerone hybrids possess drug-likeness properties with no mutagenicity/cardiotoxicity.

CONCLUSION

Zingerone hybrid (11) displayed potent anticancer and COX-2 inhibitory activity, with favorable pharmacokinetics and low toxicity.