ORIGINAL PAPER Anti-Trichomonas vaginalis activity from triterpenoid derivatives Adrine Maria Innocente & Patrícia de Brum Vieira & Amanda Piccoli Frasson & Bruna Bento Casanova & Grace Gosmann & Simone Cristina Baggio Gnoatto & Tiana Tasca Received: 10 December 2013 /Accepted: 20 May 2014 /Published online: 1 June 2014 # Springer-Verlag Berlin Heidelberg 2014 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, ther- apeutic 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 deriva- tives obtained. Compounds obtained from betulinic acid pre- sented 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 prolif- eration 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 pro- moted 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 pi- perazine 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. Keywords Triterpenes . Anti-Trichomonas vaginalis activity . Ursolic acid . Betulinic acid . Semisynthetic derivatives Introduction Trichomonas vaginalis is a flagellate protozoan that parasit- izes the human urogenital tract and causes trichomonosis, the most common non-viral sexually transmitted disease (STD) in the world with 276 million new cases each year (WHO 2012). In women, several clinical complications are associated with this infection such as cervical cancer, premature birth, low- birth-weight newborns, and pelvic inflammatory disease (Viikki et al. 2000; Cotch et al. 1997; Poole and McClelland 2013). Although among men, trichomonosis is usually asymptomatic and self-limiting, the infection has been asso- ciated to prostate cancer (Sutcliffe et al. 2006, 2012). Trichomonosis is also associated to increased transmission of HIV/AIDS (Sorvillo et al. 2001; Mason et al. 2005). Met- ronidazole and tinidazole, belonging to the 5-nitroimidazole class and approved by the Food and Drug Administration (FDA, USA), are used for the treatment of trichomonosis. However, metronidazole-resistant T. vaginalis isolates have been increasingly reported as 2.5 to 9.6 % of cases in the world (Schimdt et al. 2001; Schwebke and Barrientes 2006) leading to high drug concentration usage and toxicity risk (Petrin et al. 1998). Due to the frequency of infection on pregnancy and the development of metronidazole-resistant isolates, therapeutic alternatives to 5-nitroimidazole are ur- gently needed (Lehker and Alderete 2000). Adrine Maria Innocente and Patrícia de Brum Vieira contributed equally to this study. A. M. Innocente : B. B. Casanova : G. Gosmann : S. C. B. Gnoatto Laboratório de Fitoquímica, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, RS, Brazil P. de Brum Vieira : A. P. Frasson : T. Tasca (*) Laboratório de Pesquisa em Parasitologia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre, RS, Brazil e-mail: tiana.tasca@ufrgs.br Parasitol Res (2014) 113:2933–2940 DOI 10.1007/s00436-014-3955-0