Synthesis and biological evaluation of ursolic acid derivatives bearing triazole moieties as potential anti-Toxoplasma gondii agents

Journal of Enzyme Inhibition and Medicinal Chemistry

Guo-Hua Gong¹  Zhe-Shan Quan²  Tian Luan²  Chunmei Jin²  Chun-Mei Jin² 

[1] First Clinical Medical College of Inner Mongolia University for Nationalities, Tongliao, China;Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Inner Mongolia University for Nationalities, Tongliao, Chin;Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin, China;

关键词: Toxoplasma gondii;    ursolic acid;    molecular docking;    TgCDPK1;    in vivo;    in vitro;   

DOI  :  10.1080/14756366.2019.1584622

来源: publisher

【 摘 要 】

Ursolic acid (UA), a plant-derived compound, has many properties beneficial to health. In the present study, we synthesised three series of novel UA derivatives and evaluated their anti-Toxoplasma gondii activity both in vitro and in vivo. Most derivatives exhibited an improved anti-T. gondii activity in vitro when compared with UA (parent compound), whereas compound 3d exhibited the most potent anti-T. gondii activity in vivo. Spiramycin served as the positive control. Additionally, determination of biochemical parameters, including the liver and spleen indexes, indicated compound 3d to effectively reduce hepatotoxicity and significantly enhance anti-oxidative effects, as compared with UA. Furthermore, our molecular docking study indicated compound 3d to possess a strong binding affinity for T. gondii calcium-dependent protein kinase 1 (TgCDPK1). Based on these findings, we conclude that compound 3d, a derivative of UA, could act as a potential inhibitor of TgCDPK1.

【 授权许可】

CC BY