Design, Synthesis, and Biological Evaluation of Triazolopyrimidine–Isatin Hybrids as Promising Candidates for Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is a highly aggressive subtype marked by pronounced intra-tumoral heterogeneity and frequent therapeutic resistance. In this study, we report the design, synthesis, and biological evaluation of a novel series of triazolopyrimidine–isatin hybrids against the TNBC cell lines MDA-MB-231 and MDA-MB-468. Among them, 9h emerged as the most promising candidate, exhibiting potent cytotoxic activity against TNBC cell lines. Notably, 9h demonstrated 5.7-fold greater potency than tamoxifen and slightly better efficacy than the reference drug cisplatin against MDA-MB-231 cells. Further, 9h induced a significant reduction in MDA-MB-231 cell viability through caspase-mediated apoptosis. Preliminary ADMET predictions were also carried out to assess pharmacokinetic properties.