title: In vitro and in vivo evaluation of the antidiabetic activity of ursolic acid derivatives.
abstract: In this study, a series of ursolic acid derivatives were synthesized, and their structures were confirmed. The activity of the synthesized compounds against α-glucosidase was determined in vitro. The results suggested that all compounds have significant inhibitory activity, especially compounds 3-5 and 8, the IC50 values of which were 2.66 ± 0.84, 1.01 ± 0.44, 3.26 ± 0.22, and 3.24 ± 0.21 μM. These compounds were more potent than acarbose (positive control) against α-glucosidase. Kinetic studies were performed to determine the mechanism of inhibition by compounds 3-5 and 8. The kinetic inhibition studies indicated that compound 3 was a non-competitive inhibitor, and the inhibition constant Ki was calculated to be 2.67 ± 0.19 μM. Moreover, the kinetic inhibition studies of compounds 4, 5 and 8 demonstrated that they were mixed-type inhibitors. Furthermore, the actual pharmacological potentials of synthesized compounds 3 and 4 were demonstrated by the reduction of postprandial blood glucose levels in normal Kunming mice. The hypoglycemic effects of these compounds were more evident 30 and 60 min after maltose ingestion (P < 0.05), which was similar to the effect displayed by the positive control, acarbose.
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, PR China. Electronic address: wyuwpp@126.com.
authors.forename: Pan-Pan
authors.initials: PP
authors.lastname: Wu
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, PR China. Electronic address: kzhang@gdut.edu.cn.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, PR China. Electronic address: luyj@gdut.edu.cn.
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Lu
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, PR China. Electronic address: hepingjyjy@sina.com.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, PR China. Electronic address: sqzhao@gdut.edu.cn.
authors.forename: Su-Qing
authors.initials: SQ
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology*; D000520:alpha-Glucosidases / Q000378:metabolism; D000097245:Ursolic Acid
chemical_list: D001786:Blood Glucose; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D014315:Triterpenes; D000520:alpha-Glucosidases; D000097245:Ursolic Acid
keywords: Anti-diabetic; Synthesis; Ursolic acid derivatives; α-glucosidase inhibition