Anti-Trichomonas vaginalis Activity of Triterpenes from Tagetes nelsonii Greenm

<b>Background:</b> <i>Trichomonas vaginalis</i> is the causative agent of human trichomoniasis, the most common non-viral sexually transmitted infection. This disease is associated with an increased susceptibility to HIV and HPV infections. Currently, resistance to metronidazole (MTZ), the main drug used for treatment, has been reported in up to 9.6% of cases; additionally, the compound is also associated with adverse side effects. Therefore, it is urgent to identify new treatment options. <b>Objective</b>: In this study, we investigated for the first time the in vitro and in silico activity against <i>T. vaginalis</i> of betulin and stigmasterol isolated from <i>Tagetes nelsonii</i> Greenm, as well as their hemolytic activity. <b>Methods:</b> Plant specimen was collected in Chiapas, Mexico. Hexane and methanol extracts were prepared through sonication-assisted maceration. The antiprotozoal and hemolytic activities were evaluated in vitro against <i>Trichomonas vaginalis</i> trophozoites and human erythrocytes. The most active extract was fractionated using chromatographic techniques in a bioassay-guided study. The active metabolites were identified by ¹H and ¹³C-NMR spectroscopy, and their biological activity was further assessed in silico against lactate dehydrogenase (LDH), pyruvate ferredoxin oxidoreductase (PFOR) methionine gamma-lyase (MGL) and purine nucleoside phosphorylase (PNP) <i>T. vaginalis</i> enzymes. <b>Results:</b> Both triterpenes showed anti-trichomonal activity and no hemolytic activity at 100 µg/mL. Molecular docking studies predicted promising interactions of triterpenes with <i>T. vaginalis</i> drug target proteins, TvpFOR and TvLDH. <b>Conclusions:</b> Our results revealed that betulin and stigmasterol are potential molecules for the development of new trichomonacidal therapies against <i>T. vaginalis</i>.