LAUSR

Abstract We synthesized a new series of 1,3,4-thiadiazoline−coumarin hybrid compounds that contain d -glucose and d -galactose moieties (9a-g) and evaluated their cytotoxic activity against breast adenocarcinoma (MCF-7), human liver cancer (HepG2), human cervical cancer (HeLa), human melanoma cancer (SK-Mel-2), and human lung cancer (LU-1) cells. To reveal their selectivity toward cancer cells, the compounds were also tested against human fibroblast cell line, MRC-5. Synthesized compounds exhibited potent cytotoxic activity against the tested cell lines with IC50 values of 1.18−11.81, 1.72−9.43, 1.98−13.16, 1.82−11.25, and 2.25−14.62 μM (against MCF-7, HepG2, HeLa, SK-Mel-2, and LU-1 cells, respectively) compared to Sorafenib, 5-FU, and DOX. The long and branched-terminal carbon chains often increased activity. Interestingly, compounds 9a-g displayed selectivity toward cancer cell lines over MRC-5 (IC50 3.93−25.55 μM). These compounds also displayed potent inhibitory activity against EGFR and HER2 kinases (IC50 0.22−0.47 and 0.13−0.35 μM, respectively) compared to the standard drug, Sorafenib (IC50 = 0.11 and 0.13 μM, respectively). Molecular docking study also employed to identify the structural features required for the EGFR/HER2 inhibitory activity of the new series.