Anti-Trichomonas vaginalis activity of betulinic acid derivatives

Caused by Trichomonas vaginalis, trichomoniasis is the most common non-viral STD worldwide. Currently, metronidazole and tinidazole are the only drugs approved for treatment of the condition. However, problems such as metronidazole-resistant T. vaginalis isolates and allergic reactions have been reported. Based on data previously published by our group, structural changes in betulinic acid (1) were performed, generating three new compounds that were tested for in vitro anti-T.vaginalis activity in this study. Whereas derivative 2 did not demonstrate anti-T. vaginalis activity, derivatives 3 and 4 reduced trophozoite viability by 100%, with MIC values of 50μM. The structural difference of two compounds was performed only on the C-28 position. Derivative 3 showed low cytotoxicity against Vero cells in 24h; however, derivative 4 was highly cytotoxic, but efficient when associated with metronidazole in the synergism assay. ROS production by neutrophils was reduced, and derivative 3 showed anti-inflammatory effect. Collectively, the results of this study provide in vitro evidence that betulinic acid derivatives 3 and 4 are potential compounds with anti-T. vaginalis activity.