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

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 mu M and selectivity index (SI = 64.66) value close to that of celecoxib (IC50 = 0.93 mu M, SI = 65.47). Taken together, these results could suggest a promising chemotype for development of new COX-2-targeting anti-inflammatory agent. [GRAPHICS] .

Automated summary

By appending 1,2,3-triazole moieties on ursolic acid, three series of compounds were designed and synthesized to discover novel anti-inflammatory agents. The compound 11b exhibited the strongest anti-inflammatory activity, with molecular docking results revealing the rationale for its interaction with COX-2 enzyme, showing promise for the development of new COX-2-targeting anti-inflammatory agents.