Design, synthesis, evaluation, and molecular docking of ursolic acid derivatives containing a nitrogen heterocycle as anti-inflammatory agents
Zhi-Yu Wei, Ke-Qiang Chi, Ke-Si Wang, Jie Wu, Li-Ping Liu, Hu-Ri Piao
Index: 10.1016/j.bmcl.2018.04.021
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Abstract
Ursolic acid derivatives containing oxadiazole, triazolone, and piperazine moieties were synthesized in an attempt to develop potent anti-inflammatory agents. Structures of the synthesized compounds were elucidated by 1H NMR, 13C NMR, and HRMS. Most of the synthesized compounds showed pronounced anti-inflammatory effects at 100 mg/kg. In particular, compound 11b, which displayed the most potent anti-inflammatory activity of all of the compounds prepared, with 69.76% inhibition after intraperitoneal administration, was more potent than the reference drugs indomethacin and ibuprofen. The cytotoxicity of the compounds was also assessed by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and no compounds showed any appreciable cytotoxic activity (IC50 > 100 μmol/L). Furthermore, molecular docking studies of the synthesized compounds were performed to rationalize the obtained biological results. Overall, the results indicate that compound 11b could be a therapeutic candidate for the treatment of inflammation.