Discovery of New Non-Symmetrical Heterocyclic Pentanoid Derivatives Targeting Metastatic Triple-Negative Breast Cancer.

This study describes the synthesis and structure-activity relationship (SAR) analysis of non- symmetrical heterocyclic pentanoid derivative as potential anti-cancer agents. The lead compound, 5d, exhibited potent (IC50 = 0.38 ± 0.05 μM) and selective (Selectivity Index: 2-9) growth inhibitory effects on the metastatic triple-negative breast cancer (TNBC) cells. Mechanistic studies revealed that 5d attenuates proteasomal degradation activity via the ubiquitin-proteasome pathway, leading to G2/M phase cell cycle arrest and the induction of apoptotic cell death.