Novel thiazoline–coumarin hybrid compounds containing sugar moieties: synthesis, biological evaluation and molecular docking study as antiproliferative agents

Abstract

A new series of 2,3-thiazoline–coumarin hybrid compounds that contained D-glucose and D-galactose moieties (4a–g) were synthesized and their cytotoxic activity was evaluated 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 the human fibroblast cell line MRC-5. The synthesized compounds exhibited potent cytotoxic activity against the tested cell lines with IC₅₀ values of 1.18–11.32, 1.91–9.81, 1.96–13.16, 1.35–16.12, and 2.12–15.92 μM (against MCF-7, HepG2, HeLa, SK-Mel-2, and LU-1 cells, respectively) compared with Sorafenib, doxorubicin, and 5-fluorouracil. Interestingly, compounds 4a–g displayed selectivity toward cancer cell lines over MRC-5 (IC₅₀ 3.97–25.75 μM). The most active compounds, including 4d, 4e, and 4f, also displayed potent inhibitory activity against EGFR and HER2 kinases (IC₅₀ 0.15–0.31 and 0.15–0.25 μM, respectively) compared with the standard drug Sorafenib (IC₅₀ = 0.11 and 0.13 μM, respectively). Molecular docking also showed that the hydrogen binding interactions often occurred between the CO lactone of the coumarin ring and appropriate amino acid residues, which played a key role in enhancing its potency against both enzymes.