Exploiting the Triazole–Urea Hybrid as a Privileged Scaffold for Novel Anti-HCC Agents: Discovery of a Potent Inducer of DNA Damage and Apoptosis

In the search for novel anticancer agents, a series of triazole–urea hybrids were designed and synthesized. Among them, compound 5a exhibited potent and selective cytotoxicity against hepatocellular carcinoma (HCC) cells, displaying an IC 50 value of 8.32 ± 1.26 μM against the Huh-7 cell line, while exerting minimal effects on other cancer cell lines and normal hepatocytes (LO2). Mechanistic investigations revealed that 5a triggers DNA damage and activates autophagy, which collectively contribute to the suppression of cell proliferation and the induction of dose-dependent apoptosis. Taken together, 5a represents a promising lead compound for the development of novel anti-HCC therapeutics, warranting further in-depth evaluation.