期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 116, 期 -, 页码 102-115出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2016.03.050
关键词
C-5-curcuminoid; Hybrid; Coumarin; Antitumor; Antitubulin; Docking
资金
- University Grants Commission
Keeping in view the confines allied with presently accessible antitumor agents and success of C-5-curcuminoid based bifunctional hybrids as novel antitubulin agnets, molecular hybrids of C-5-curcuminoid and coumarin tethered by triazole ring have been synthesized and investigated for in-vitro cytotoxicity against THP-1, COLO-205, HCT-116 and PC-3 human tumor cell lines. The results revealed that the compounds A-2 to A-9, B-2, B-3, B-7 showed significant cytotoxic potential against THP-1, COLO-205 and HCT-116 cell lines, while the PC-3 cell line among these was found to be almost resistant. Structure activity relationship revealed that the nature of Ring X and the length of carbon-bridge (n) connecting triazole ring with coumarin moiety considerably influence the activity. Methoxy substituted phenyl ring as Ring X and two carbon-bridges were found to be the ideal structural features. The most potent compounds (A-2, A-3 and A-7) were further tested for tubulin polymerization inhibition. Compound A-2 was found to significantly inhibit the tubulin polymerization (IC50 = 0.82 mu M in THP-1 tumor cells). The significant cytotoxicity and tubulin polymerization inhibition by A-2 was further rationalized by docking studies where it was docked at the curcumin binding site of tubulin. (C) 2016 Elsevier Masson SAS. All rights reserved.
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