Novel Flavonoids with Antiproliferative Activities against Breast Cancer Cells

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• 作者：Nianhuan Yao ; Chao-Yu Chen ; Chun-Yi Wu ; Kiyomi Motonishi ; Hsing-Jien Kung ; Kit S. Lam
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：July 14, 2011
• 年：2011
• 卷：54
• 期：13
• 页码：4339-4349
• 全文大小：1064K
• 年卷期：v.54,no.13(July 14, 2011)
• ISSN：1520-4804

文摘

A series of flavone analogues were synthesized and evaluated for their antiproliferation activity against breast cancer cells. The IC₅₀ of compound 10 and 24 were determined to be at 5 渭M. These compounds were used as baits to screen breast cancer cDNA expression phage display proteome library. DNA sequencing of the binding phages suggests that eEF1A1 is a target protein for 10 and 24. Further optimization of these compounds led to the discovery of 39 with higher cytotoxic potency (IC₅₀ = 1 渭M) and binding to eEF1A2. Biological and biochemical data suggest that eEF1A2 might be a therapeutic target and that 39 is an excellent lead compound for further development.