title: Inhibitory activity of flavonoids against class I phosphatidylinositol 3-kinase isoforms.
abstract: 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.
authors.affiliation: School of Pharmaceutical Sciences and Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. kongdexin@tijmu.edu.cn
authors.forename: Dexin
authors.initials: D
authors.lastname: Kong
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Zhang
authors.forename: Takao
authors.initials: T
authors.lastname: Yamori
authors.forename: Hongquan
authors.initials: H
authors.lastname: Duan
authors.forename: Meihua
authors.initials: M
authors.lastname: Jin
mesh_terms: D058534:Class I Phosphatidylinositol 3-Kinases / Q000037:antagonists & inhibitors*; D004789:Enzyme Activation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D007527:Isoenzymes; D058534:Class I Phosphatidylinositol 3-Kinases