Design, Synthesis, Anti-Proliferative, and Apoptotic Assessment of Spirocyclopropyl Oxindole–Isatin Hybrids on Triple-Negative Breast Cancer

A series of 1H-1,2,3-triazole-tethered spirocyclopropyl oxindole–isatin hybrids were synthesized using a copper-promoted click reaction and evaluated for their anti-proliferative activities against triple-negative breast cancer cell lines. The most potent compound in the series outperformed tamoxifen and 5-fluorouracil, with selectivity indices of 1.60 and 1.99 against MDA-MB-468 and MDA-MB-231 cancer cells, respectively. The Caspase 3/7 7-AAD assay showed live cell populations of 72.10% and 49.20% after 24 and 48 h, respectively, indicating that the cytotoxic effect is mediated through the caspase apoptotic pathway. Molecular docking studies further suggested the compound's potential as an epidermal growth factor receptor inhibitor, highlighting its promise as a therapeutic agent.