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

Title:Synthesis and Evaluation of 4-arylmethyl Curcumin Analgues as Potent Hsp90 Inhibitors

Volume: 11 Issue: 8

Author(s): Yang Liu, Min Ye, Qundan Wu, Lixian Wu and Jianhua Xu

Affiliation:

Keywords: 4-Arylmethyl curcumin analogue, Breast cancer, Curcumin, Hsp90, Hsp90 inhibitors, Molecular docking.

Abstract: 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.

Cite this article as:

Liu Yang, Ye Min, Wu Qundan, Wu Lixian and Xu Jianhua, Synthesis and Evaluation of 4-arylmethyl Curcumin Analgues as Potent Hsp90 Inhibitors, Letters in Drug Design & Discovery 2014; 11 (8) . https://dx.doi.org/10.2174/1570180811666140512221037

DOI https://dx.doi.org/10.2174/1570180811666140512221037	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X