title: Anti-Trichomonas vaginalis activity from triterpenoid derivatives.
abstract: Trichomonas vaginalis is a flagellated parasite that causes trichomonosis, the most common non-viral sexually transmitted disease (STD) in the world. Worryingly, trichomonosis is associated to increased transmission of HIV. Due to high frequency of the infection during pregnancy and the development of metronidazole-resistant isolates, therapeutic alternatives to 5-nitroimidazole are being searched. Triterpenes are natural products presenting several biological activities such as anti-protozoal activity. The aim of this study was to evaluate the in vitro anti-T. vaginalis activity from betulinic and ursolic acids, as well as semisynthetic derivatives obtained. Compounds obtained from betulinic acid presented better activity than those from ursolic acid. Piperazine derivatived from betulinic acid presented minimum inhibitory concentration (MIC) value of 91.2 μM, and the kinetic growth curve performed with parasites treated with this most active compound revealed complete inhibition of trophozoite proliferation at 2 h of incubation and total abolition of trophozoite growth in 24 h, revealing that the piperazine derivative is an efficient trichomonacidal molecule. The same compound promoted total erythrocyte lysis and lactate dehydrogenase (LDH) liberation of 83 and 100% (at 45.6 and 91.2 μM, respectively), indicating parasite membrane damage. The piperazine derivative demonstrated cytotoxic effect against the HMVII and HeLa cell lineages at the MIC value. This is the first report of semisynthetic triterpenoid derivatives with anti-T. vaginalis activity, revealing the high potential of these compounds as trichomonacidal agents.
authors.affiliation: Laboratório de Fitoquímica, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, RS, Brazil.
authors.forename: Adrine Maria
authors.initials: AM
authors.lastname: Innocente
authors.forename: Patrícia de Brum
authors.initials: Pde B
authors.lastname: Vieira
authors.forename: Amanda Piccoli
authors.initials: AP
authors.lastname: Frasson
authors.forename: Bruna Bento
authors.initials: BB
authors.lastname: Casanova
authors.forename: Grace
authors.initials: G
authors.lastname: Gosmann
authors.forename: Simone Cristina Baggio
authors.initials: SC
authors.lastname: Gnoatto
authors.forename: Tiana
authors.initials: T
authors.lastname: Tasca
mesh_terms: D000994:Antitrichomonal Agents / Q000494:pharmacology*; D004351:Drug Resistance; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006367:HeLa Cells; D006461:Hemolysis; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D053978:Pentacyclic Triterpenes; D000077489:Piperazine; D010879:Piperazines / Q000494:pharmacology; D014246:Trichomonas vaginalis / Q000187:drug effects* / Q000254:growth & development; D014315:Triterpenes / Q000494:pharmacology*; D000094062:Betulinic Acid; D000097245:Ursolic Acid
chemical_list: D000994:Antitrichomonal Agents; D008795:Metronidazole; D053978:Pentacyclic Triterpenes; D000077489:Piperazine; D010879:Piperazines; D014315:Triterpenes; D000094062:Betulinic Acid; D000097245:Ursolic Acid