Synthesis, structure-activity relationship and molecular docking studies of novel quinoline-chalcone hybrids as potential anticancer agents and tubulin inhibitors
Abstract
A new series of quinoline-chalcone hybrids was synthesized. The structures of these compounds were characterized by spectroscopic methods including 1H and 13CNMR and mass spectroscopy. The cytotoxic activity of compounds was evaluated against four human cancer cell lines including A2780 (human ovarian carcinoma) and A2780/RCIS (Cisplatin resistant human ovarian carcinoma), MCF-7 (human breast cancer cells), MCF-7/MX (Mitoxantrone resistant human breast cancer cells) and normal Huvec cells. The structure-activity relationship of synthesized compounds is discussed. Among quinolines 5e, 5g and 5j possessing benzoyl group showed significant cytotoxic activity against both resistant cancer cells and their parents. Compounds 5g and 5j, demonstrated the most antiproliferative activity with IC50 values ranging from 2.32 to 22.4 μM. They were also identified as tubulin inhibitors and induced cell cycle arrest at G2/M phase and apoptosis. Compound 5j induced more arrest at G2/M phase in four cancer cell lines compared to compound 5g. Finally, molecular dynamics simulation and molecular docking studies of compound 5j into the colchicine-binding site of tubulin demonstrated the possible interaction of this compound in the active site of tubulin.
- Publication:
-
Journal of Molecular Structure
- Pub Date:
- February 2020
- DOI:
- 10.1016/j.molstruc.2019.127310
- Bibcode:
- 2020JMoSt120227310M
- Keywords:
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- Chalcone;
- Quinoline;
- Structure-activity relationship;
- Tubulin inhibitors;
- Anticancer activity;
- Molecular docking;
- Resistant cancer cells