Synthesis and Evaluation of 4-arylmethyl Curcumin Analgues as Potent Hsp90 Inhibitors
Yang Liu, Min Ye, Qundan Wu, Lixian Wu and Jianhua Xu
Affiliation: School of Pharmacy, Fujian Medical University, 1 Xue Yuan Road, University Town, Fuzhou, China.
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.
Keywords: 4-Arylmethyl curcumin analogue, Breast cancer, Curcumin, Hsp90, Hsp90 inhibitors, Molecular docking.
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