New ursolic acid derivatives bearing 1,2,3-triazole moieties: design, synthesis and anti-inflammatory activity in vitro and in vivo.

Autor: Zhang TY; Jilin Medical University, Jilin, 132013, Jilin Province, People's Republic of China., Li CS; The Third People's Hospital of Dalian, Dalian, 116000, People's Republic of China., Cao LT; Jilin Medical University, Jilin, 132013, Jilin Province, People's Republic of China., Bai XQ; Jilin Medical University, Jilin, 132013, Jilin Province, People's Republic of China., Zhao DH; Jilin Medical University, Jilin, 132013, Jilin Province, People's Republic of China. donghaizhao2021@126.com., Sun SM; Zhoushan Hospital, Zhejiang University School of Medicine, Zhoushan, 316021, Zhejiang Province, People's Republic of China. sunsimei1024@163.com.
Jazyk: angličtina
Zdroj: Molecular diversity [Mol Divers] 2022 Apr; Vol. 26 (2), pp. 1129-1139. Date of Electronic Publication: 2021 Jun 02.
DOI: 10.1007/s11030-021-10236-0
Abstrakt: In order to discover novel anti-inflammatory agents, three series of compounds obtained by appending 1,2,3-triazole moieties on ursolic acid were designed and synthesized. All compounds have been screened for their anti-inflammatory activity by using an ear edema model. The potent anti-inflammatory compound was subjected to in vitro cyclooxygenase COX-1/COX-2 inhibition assays. In general, the derivatives were found to be potent anti-inflammatory activity. Especially, the compound 11b exhibited the strongest activity of all of the compounds prepared, with 82.81% inhibition after intraperitoneal administration, which was better than celecoxib as a positive control. Molecular docking results unclose the rationale for the interaction of the compound 11b with COX-2 enzyme. Further studies revealed that compound 11b exhibited effective COX-2 inhibitory activity, with half-maximal inhibitor concentration (IC 50 ) value of 1.16 µM and selectivity index (SI = 64.66) value close to that of celecoxib (IC 50  = 0.93 µM, SI = 65.47). Taken together, these results could suggest a promising chemotype for development of new COX-2-targeting anti-inflammatory agent.
(© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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