Inhibitory Activity of Flavonoids against Class I Phosphatidylinositol 3-Kinase Isoforms

Molecules

Dexin Kong¹  Yanwen Zhang¹  Takao Yamori¹  Hongquan Duan¹ 

[1] ¹School of Pharmaceutical Sciences and Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China ²Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-10-6, Ariake, Koto-ku, Tokyo 135-8550, Japan

关键词: phosphatidylinositol 3-kinase;    flavonoid;    structure-activity relationship;   

DOI  :  10.3390/molecules16065159

来源: mdpi

【 摘 要 】

Class I PI3 Kinase (PI3K) phosphorylates phosphatidylinositol 4,5-bisphophate (PIP2) to generate the second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3) and therefore plays an important role in fundamental cellular responses such as proliferation. There are four isoforms of class I PI3K which are known to have different functions and relate to various diseases such as cancer and inflammation. Flavonoids are abundant in fruits, vegetables and plant-derived beverages such as tea. So far, various pharmacological effects of flavonoids have been reported. We previously reported that the flavonoid baicalein exhibits potent PI3K-inhibitory activity. Recently we examined the inhibitory activity of eighteen flavonoids against PI3Ka by using an in vitro homogenous time resolved fluorescence (HTRF) kinase assay, and deduced their structure-activity relationships by comparing the activities of the analogues. Our result suggests that the number of hydroxyl groups in the A and B rings might promote the activity, while loss of C2-C3 double bond might reduce the activity. Furthermore, the activity against 4 class I PI3K isoforms of some selected flavonoids was investigated, and the results indicate that the flavonoids seem to exhibit more potent activity on PI3Ka and d isoforms compared with that on PI3Kb and g isoforms.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.