title: Identification of pentacyclic triterpenes derivatives as potent inhibitors against glycogen phosphorylase based on 3D-QSAR studies.
abstract: Naturally occurring pentacyclic triterpenes (PT), a novel class of inhibitors against glycogen phosphorylase (GP), hold promise for the treatment of type-2 diabetes and other diseases with disorders in glycogen metabolism. To identify novel and more potent GP inhibitors, the receptor-based comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) approaches were performed to investigate the quantitative structure-activity relationships (QSAR) among 106 PT analogues. The validated models demonstrated that the elongated or bulky substitutions in C17 position and/or C2, C3 positions are favorable. Then based on the structural information extracted from these models, 56 derivatives were synthesized and biochemically tested in this study. The IC50 value of the most potent compound P50 was found to be 1.1 μM.
authors: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors: Zhongjie
authors: Z
authors: Liang
authors: Liying
authors: L
authors: Zhang
authors: Lianchun
authors: L
authors: Li
authors: Jun
authors: J
authors: Liu
authors: Hongling
authors: H
authors: Li
authors: Luyong
authors: L
authors: Zhang
authors: Limin
authors: L
authors: Chen
authors: Keguang
authors: K
authors: Cheng
authors: Mingyue
authors: M
authors: Zheng
authors: Xiaoan
authors: X
authors: Wen
authors: Pu
authors: P
authors: Zhang
authors: Jia
authors: J
authors: Hao
authors: Yanchun
authors: Y
authors: Gong
authors: Xia
authors: X
authors: Zhang
authors: Xiaoyun
authors: X
authors: Zhu
authors: Jun
authors: J
authors: Chen
authors: Hong
authors: H
authors: Liu
authors: Hualiang
authors: H
authors: Jiang
authors: Cheng
authors: C
authors: Luo
authors: Hongbin
authors: H
authors: Sun
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D024982:Glycogen Phosphorylase, Muscle Form / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D018482:Muscle, Skeletal / Q000201:enzymology; D053978:Pentacyclic Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D011817:Rabbits; D013237:Stereoisomerism
chemical_list: D004791:Enzyme Inhibitors; D053978:Pentacyclic Triterpenes; D024982:Glycogen Phosphorylase, Muscle Form