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

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Abstract

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 (IC50) value of 1.16 µM and selectivity index (SI = 64.66) value close to that of celecoxib (IC50 = 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.

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Acknowledgements

This research was supported by the Natural Science Foundation of Jilin Province (No.20190201148JC); the Department of Education of Jilin Province (No.JJKH20200461KJ and JJKH20210495KJ); and the Public Welfare Project of Zhoushan Municipal Science and Technology Bureau, Zhejiang Province (No. 2020C31044).

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  1. Tian-Yi Zhang and Chun-Shi Li have contributed equally to this work.

Authors and Affiliations

  1. Jilin Medical University, Jilin, 132013, Jilin Province, People’s Republic of China

    Tian-Yi Zhang, Li-Ting Cao, Xue-Qian Bai & Dong-Hai Zhao

  2. Zhoushan Hospital, Zhejiang University School of Medicine, Zhoushan, 316021, Zhejiang Province, People’s Republic of China

    Si-Mei Sun

  3. The Third People’s Hospital of Dalian, Dalian, 116000, People’s Republic of China

    Chun-Shi Li

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Zhang, TY., Li, CS., Cao, LT. et al. New ursolic acid derivatives bearing 1,2,3-triazole moieties: design, synthesis and anti-inflammatory activity in vitro and in vivo. Mol Divers 26, 1129–1139 (2022). https://doi.org/10.1007/s11030-021-10236-0

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