title: Caatinga plants: Natural and semi-synthetic compounds potentially active against Trichomonas vaginalis.
abstract: Trichomonas vaginalis causes trichomoniasis; the most common but overlooked non-viral sexually transmitted disease worldwide. The treatment is based at 5'-nitroimidazoles, however, failure are related to resistance of T. vaginalis to chemotherapy. Caatinga is a uniquely Brazilian region representing a biome with type desert vegetation and plants present diverse biological activity, however, with few studies. The aim of this study was to investigate the activity against T. vaginalis of different plants from Caatinga and identify the compounds responsible by the activity. A bioguided fractionation of Manilkara rufula was performed and four major compounds were identified: caproate of α-amyrin (1b), acetate of β-amyrin (2a), caproate of β-amyrin (2b), and acetate of lupeol (3a). In addition, six derivatives of α-amyrin (1), β-amyrin (2) and lupeol (3) were synthesized and tested against the parasite. Ursolic acid (5) reduced about 98% of parasite viability after 2h of incubation and drastic ultrastructural alterations were observed by scanning electron microscopy. Moreover, 5 presented high cytotoxicity to HMVII and HeLa cell line and low cytotoxicity against Vero line at 50 μM (MIC against the parasite). Metronidazole effect against T. vaginalis resistant isolate was improved when in association with 5.
authors.affiliation: Laboratório de Pesquisa em Parasitologia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil. Electronic address: patriciasbrum@yahoo.com.br.
authors.forename: Patrícia de Brum
authors.initials: Pde B
authors.lastname: Vieira
authors.affiliation: Laboratório de Pesquisa em Parasitologia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil. Electronic address: nicolaslfsilva@gmail.com.
authors.forename: Nícolas Luiz Feijó
authors.initials: NL
authors.lastname: Silva
authors.affiliation: Laboratório de Fitoquímica e Síntese Orgânica, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil. Electronic address: narjarags@gmail.com.
authors.forename: Gloria Narjara Santos
authors.initials: GN
authors.lastname: da Silva
authors.affiliation: Laboratório de Produtos Naturais e Espectrometria de Massas (LAPNEM), Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, MS 79090-900, Brazil; Núcleo de Pesquisas em Produtos Naturais e Sintéticos, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP 14040-903, Brazil. Electronic address: denise.brentan@ufms.com.
authors.forename: Denise Brentan
authors.initials: DB
authors.lastname: Silva
authors.affiliation: Núcleo de Pesquisas em Produtos Naturais e Sintéticos, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP 14040-903, Brazil. Electronic address: npelopes@fcfrp.usp.b.
authors.forename: Norberto Peporine
authors.initials: NP
authors.lastname: Lopes
authors.affiliation: Laboratório de Fitoquímica e Síntese Orgânica, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil. Electronic address: simone.gnoatto@ufrgs.br.
authors.forename: Simone Cristina Baggio
authors.initials: SC
authors.lastname: Gnoatto
authors.affiliation: Centro de Ciências Biológicas e Departamento de Bioquímica, Universidade Federal de Pernambuco, Recife, PE 50670-901, Brazil. Electronic address: Marcia.vanusa@ufpe.br.
authors.forename: Márcia Vanusa
authors.initials: MV
authors.lastname: da Silva
authors.affiliation: Faculdade de Farmácia e Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil; Instituto Nacional do Semi-Árido (INSA), Núcleo de Biprospecção da Caatinga (NBioCaat), Campina Grande, Pernambuco, Brazil. Electronic address: Alexandre.jose.macedo@gmail.com.
authors.forename: Alexandre José
authors.initials: AJ
authors.lastname: Macedo
authors.affiliation: Department of Natural Products, Plant Biology and Soil Science, Faculty of Pharmacy, University of Barcelona, Barcelona, Catalonia 08028, Spain. Electronic address: jaumebastida@ub.edu.
authors.forename: Jaume
authors.initials: J
authors.lastname: Bastida
authors.affiliation: Laboratório de Pesquisa em Parasitologia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil; Instituto Nacional do Semi-Árido (INSA), Núcleo de Biprospecção da Caatinga (NBioCaat), Campina Grande, Pernambuco, Brazil. Electronic address: tiana.tasca@ufrgs.br.
authors.forename: Tiana
authors.initials: T
authors.lastname: Tasca
mesh_terms: D004353:Drug Evaluation, Preclinical; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry* / Q000145:classification; D014246:Trichomonas vaginalis / Q000187:drug effects*
chemical_list: D010936:Plant Extracts
keywords: Caatinga plants; Cytotoxicity; Trichomonas vaginalis; Triterpenes; Ursolic acid