Total Synthesis of Hispidulin and the Structural Basis for Its Inhibition of Proto-oncogene Kinase Pim-1
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- 作者：Shi-Wei Chao ; Ming-Yuan Su ; Lih-Chu Chiou ; Liang-Chieh Chen ; Chung-I Chang ; Wei-Jan Huang
- 刊名：Journal of Natural Products
- 出版年：2015
- 出版时间：August 28, 2015
- 年：2015
- 卷：78
- 期：8
- 页码：1969-1976
- 全文大小：491K
- ISSN：1520-6025
文摘
A new method is applied to synthesize hispidulin, a natural flavone with a broad spectrum of biological activities. Hispidulin exhibits inhibitory activity against the oncogenic protein kinase Pim-1. Crystallographic analysis of Pim-1 bound to hispidulin reveals a binding mode distinct from that of quercetin, suggesting that the binding potency of flavonoids is determined by their hydrogen-bonding interactions with the hinge region of the kinase. Overall, this work may facilitate construction of a library of hispidulin-derived compounds for investigating the structure鈥揳ctivity relationship of flavone-based Pim-1 inhibitors.