title: Synthesis and biological evaluation of novel ursolic acid analogues as potential α-glucosidase inhibitors.
abstract: Ursolic acid (UA) is a major pentacyclic triterpenoid in plants, vegetables and fruits, which has been reported to have a potential anti-diabetic activity. Despite various semi-synthetic ursolic acid derivatives already described, new derivatives still need to be designed and synthesized to further improve the anti-diabetic activity. In the present study, two series of novel UA derivatives, were synthesized and their structures were confirmed. The enzyme inhibition activities of semi-synthesized analogues against α-glucosidase were screened in vitro. The results indicated that most of UA derivatives showed a significant inhibitory activity, especially analogues UA-O-i with the IC50values of 0.71 ± 0.27 μM, which was more potential than other analogues and the positive control. Furthermore, molecular docking studies were also investigated to verify the in vitro study. Structure modification at the C-3 and C-2 positions of UA was an effective approach to obtain the desired ligand from UA, whose structure was in accordance with the active pocket. Besides, suitable hydrophobic group at the position of C-2 might play an important role for the docking selectivity and binding affinity between the ligand and the homology modelling protein. These results could be helpful for designing more potential α-glucosidase inhibitors from UA in the future.
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, China.|Faculty of Chemical &Environmental Engineering, Wuyi University, Jiangmen, 529020, China.|International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529020, China.
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, China.
authors.forename: Bing-Jie
authors.initials: BJ
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, China.
authors.forename: Xi-Ping
authors.initials: XP
authors.lastname: Cui
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, China.
authors.forename: Zheng-Yun
authors.initials: ZY
authors.lastname: Jiang
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Zhou
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Zhong
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, China.
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Mai
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Ouyang
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, China.
authors.forename: Hui-Sheng
authors.initials: HS
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, 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, 510006, China.|International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529020, China.
authors.forename: Su-Qing
authors.initials: SQ
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, China.|Faculty of Chemical &Environmental Engineering, Wuyi University, Jiangmen, 529020, China.|International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529020, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
mesh_terms: D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D014315:Triterpenes; D000097245:Ursolic Acid