title: Synthesis and biological evaluation of ambradiolic acid as an inhibitor of glycogen phosphorylase.
abstract: Ambradiolic acid (3) with oleanane skeleton is a natural pentacyclictriterpene. The first synthesis of 3 starting from 23-hydroxybetulinic acid (2) has been accomplished in 12-steps with a total yield of 18.1% in our study. Compound 3 was further biologically evaluated and found to exhibit significant inhibitory activity against rabbit muscle glycogen phosphorylase (GP) with an IC50 value of 12.4 μM, suggesting it could be a potential lead compound for the development of hypoglycemic drugs.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China; Department of Organic Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China; Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Hengyuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China; Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Peiqing
authors.initials: P
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China; Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China; Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Hequan
authors.initials: H
authors.lastname: Yao
authors.affiliation: Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, PR China.
authors.forename: Wencai
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA.
authors.forename: Jieyun
authors.initials: J
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China; Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China. Electronic address: jinyixu@china.com.
authors.forename: Jinyi
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D018482:Muscle, Skeletal / Q000201:enzymology; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D053978:Pentacyclic Triterpenes / Q000138:chemical synthesis / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry
chemical_list: C468651:23-hydroxybetulinic acid; D004791:Enzyme Inhibitors; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C000597769:ambradiolic acid; C413246:oleanane; D009828:Oleanolic Acid; D024981:Glycogen Phosphorylase
keywords: 23-Hydroxybetulinic acid; Ambradiolic acid; First synthesis; Glycogen phosphorylase (GP)