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Letters in Drug Design & Discovery
ISSN (Print): 1570-1808
ISSN (Online): 1875-628X
Epub Full Text Article
DOI: 10.2174/1570180811666140512221037      Price:  $95

Synthesis and Evaluation of 4-Arylmethyl Curcumin Analgues as Potent Hsp90 Inhibitors

Author(s): Yang Liu, Min Ye, Qundan Wu, Lixian Wu and Jianhua Xu
Hsp90 is a potential target for the treatment of cancer. Curcumin is a natural product used to prevent and treat cancer. 4-(4-Hydroxy-3-methoxybenzyl) curcumin (C086), a 4-arylmethyl curcumin analogue, showed lead-like properties. Western blot analyses and molecular docking study supported C086 as an Hsp90 inhibitor. Subsequently, C086 analogues were designed, synthesized and evaluated. These compounds showed increased antiproliferative activity against SKBr3 and MCF-7 breast cancer cells. The most promising compounds 7 and 10 (IC50=1.66μM and 0.509μM) were 5-fold and 17-fold better than C086 (IC50=8.55μM) against SkBr3 cell, respectively. Her2 degradation and Hsp70 induction were observed upon administration of selected 4-arylmethyl curcumin analgues, suggesting that these compounds exerted their activity through Hsp90 inhibition.
Hsp90, Hsp90 inhibitors, Breast cancer, Curcumin, 4-Arylmethyl curcumin analogue, Molecular docking
Institute of Materia Medica School of Pharmacy Fujian Medical University Fujian Provincial Key Laboratory of Natural Medicine Pharmacology Fuzhou China.