Activity Study of Cabotegravir Derivatives Inducing Mitochondrial Apoptosis in HeLa Cells

Cervical cancer ranks as the fourth most common cancer among women. Its progression is associated with accelerated cell cycle progression and inhibition of apoptosis. Given the unique potential of cabotegravir in suppressing cervical cancer cells and the widespread application of the 1,2,3-triazole scaffold in promoting mitochondrial apoptosis, we evaluated a series of cabotegravir derivatives incorporating 1,2,3-triazole for their anticancer potential. In vitro activity assays in HeLa cells revealed that compound 4v exhibited the most potent cytotoxicity (IC50 = 3.06±0.17 μM). It significantly suppressed colony formation in a dose-dependent manner and induced marked morphological changes in HeLa cells. Further studies showed that compound 4v triggered apoptosis and caused G2/M cell cycle arrest. Western blot analysis demonstrated that 4v increased the Bax/Bcl-2 ratio, reduced levels of caspase-9, caspase-3, and PARP1, and promoted PARP1 cleavage, indicating that the mitochondrial apoptotic pathway was involved. In conclusion, compound 4v exhibited promising potential as a candidate for cervical cancer therapy.