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

New Journal of Chemistry Pub Date: 2021-05-07 DOI: 10.1039/D1NJ00680K

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 C[double bond, length as m-dash]O lactone of the coumarin ring and appropriate amino acid residues, which played a key role in enhancing its potency against both enzymes.

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