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Synthesis and evaluation of ursolic acid-based 1,2,4-triazolo[1,5-a]pyrimidines derivatives as anti-inflammatory agents

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Abstract

Here, two series of novel ursolic acid-based 1,2,4-triazolo[1,5-a]pyrimidines derivatives were synthesized and screened for their anti-inflammatory activity by evaluating their inhibition effect of using LPS-induced inflammatory response in RAW 264.7 macrophages in vitro; the effects of different concentrations of the compounds on the secretion of nitric oxide (NO) and inflammatory cytokines including TNF-α and IL-6 were evaluated. Their toxicity was also assessed in vitro. Results showed that the most prominent compound 3 could significantly decrease production of the above inflammatory factors. Docking study was performed for the representative compounds 3, UA, and Celecoxib to explain their interaction with cyclooxygenase-2 (COX-2) receptor active site. In vitro enzyme study implied that compound 3 exerted its anti-inflammatory activity through COX-2 inhibition.

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Acknowledgements

This research was supported by the Natural Science Foundation of Jilin Province (No. 20190201077JC); The Health Department of Jilin Province (No. 2019ZC007); The Doctoral Foundation of Jilin Medical University (No. JYBS2018007); and The Jilin Province Students’ Program for Innovation and Entrepreneurship Training (No. 202013706011).

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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, Ping Li, Xue-Qian Bai, Shu-Ying Guo & Ying Jin

  2. The Third People’s Hospital of Dalian, Dalian, 116000, Liaoning Province, People’s Republic of China

    Chun-Shi Li

  3. Department of General Surgery, Affiliated Hospital of Yanbian University, Yanji, 133000, Jilin Province, People’s Republic of China

    Sheng-Jun Piao

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  1. Tian-Yi Zhang
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Zhang, TY., Li, CS., Li, P. et al. Synthesis and evaluation of ursolic acid-based 1,2,4-triazolo[1,5-a]pyrimidines derivatives as anti-inflammatory agents. Mol Divers 26, 27–38 (2022). https://doi.org/10.1007/s11030-020-10154-7

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