title: Synthesis and Evaluation of Novel Triterpene Analogues of Ursolic Acid as Potential Antidiabetic Agent.
abstract: Ursolic acid (UA) is a naturally bioactive compound that possesses potential anti-diabetic activity. The relatively safe and effective molecule intrigued us to further explore and to improve its anti-diabetic activity. In the present study, a series of novel UA analogues was synthesized and their structures were characterized. Their bioactivities against the α-glucosidase from baker's yeast were determined in vitro. The results suggested that most of the analogues exhibited significant inhibitory activity, especially analogues 8b and 9b with the IC50 values of 1.27 ± 0.27 μM (8b) and 1.28 ± 0.27 μM (9b), which were lower than the other analogues and the positive control. The molecular docking and 2D-QSAR studies were carried out to prove that the C-3 hydroxyl could interact with the hydrophobic region of the active pocket and form hydrogen bonds to increase the binding affinity of ligand and the homology modelling protein. Thus, these results will be helpful for understanding the relationship between binding mode and bioactivity and for designing better inhibitors from UA analogues.
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, China.
authors.forename: Tianming
authors.initials: T
authors.lastname: Huang
authors.affiliation: Guangxi Institute of Botany, Guangxi Zhuang Autonomous Region and Chinese Academy of Sciences, Guilin, China.
authors.forename: Dianmeng
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, China.
authors.forename: Anming
authors.initials: A
authors.lastname: Cheng
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, China.
authors.forename: Zhengyun
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, China.
authors.forename: Luoying
authors.initials: L
authors.lastname: Jiao
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, China.
authors.forename: Suqing
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
mesh_terms: D020134:Catalytic Domain / Q000187:drug effects; D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006860:Hydrogen Bonding; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D021281:Quantitative Structure-Activity Relationship; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D013729:Terpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology; D000520:alpha-Glucosidases / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D000097245:Ursolic Acid
chemical_list: D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D029701:Saccharomyces cerevisiae Proteins; D013729:Terpenes; D014315:Triterpenes; D000520:alpha-Glucosidases; D000097245:Ursolic Acid