Synthesis and antiproliferative potency of 1,3,4-thiadiazole and 1,3-thiazolidine-4-one based new binary heterocyclic molecules: in vitro cell-based anticancer studies

Herein, we report the synthesis and Anticancer properties of 21 new 1,3,4-thiadiazole-2-yl-imino-thiazolidine-4-one containing binary heterocyclic molecules. Cytotoxicity of the synthesized molecules was evaluated on various in vitro Cancer cell lines (MCF-7, PC3, 4T1, MDA-MB-231, and MOC2) and normal human embryonic cell lines (HEK-293) via MTT assay. The cytotoxicity data of developed compounds was compared with the reference Anticancer molecule BG45, a selective inhibitor of the HDAC3 Enzyme. All compounds showed a significant cytotoxic effect higher than BG45 on tested Cancer cell lines. Moreover, the compounds exhibited better selectivity on Cancer cells than on normal cells. Among the molecules, compound 6e is the most potent in cytotoxic activity on MCF-7 cell lines (IC₅₀ value of 3.85 μM). Additional mechanistic investigation revealed that compound 6e promotes Apoptosis (25.3%) and G0/G1 phase cell cycle arrest of MCF-7 cells. Also, compound 6e induces intracellular ROS accumulation and subsequent nuclear fragmentation. Hence, this research finds new hybrid molecules active against in vitro Cancer cells.