title: The anti-Trichomonas vaginalis phloroglucinol derivative isoaustrobrasilol B modulates extracellular nucleotide hydrolysis.
abstract: Trichomonas vaginalis causes trichomoniasis, a neglected sexually transmitted disease. Due to severe health consequences and treatment failure, new therapeutic alternatives are crucial. Phloroglucinols from southern Brazilian Hypericum species demonstrated anti-T. vaginalis and anti-Leishmania amazonensis activities. The modulation of biochemical pathways involved in the control of inflammatory response by ectonucleotidases, NTPDase, and ecto-5'-nucleotidase represents new targets for combating protozoa. This study investigated the activity of phloroglucinol derivatives of Hypericum species from southern Brazil against T. vaginalis as well as its ability on modulating parasite ectonucleotidases and, consequently, immune parameters through ATP and adenosine effects. Phloroglucinol derivatives screening revealed activity for isoaustrobrasilol B (IC5038 μm) with no hemolytic activity. Although the most active compound induced cytotoxicity against a mammalian cell lineage, the in vivo model evidenced absence of toxicity. Isoaustrobrasilol B significantly inhibited NTPDase and ecto-5'-nucleotidase activities, and the immune modulation attributed to extracellular nucleotide accumulation was evaluated. The production of ROS and IL-6 by T. vaginalis-stimulated neutrophils was not affected by the treatment. Conversely, IL-8 levels were significantly enhanced. The associative mechanism of trophozoites death and ectonucleotidases modulation by isoaustrobrasilol B may increase the susceptibility of T. vaginalis to host innate immune cell like neutrophils consequently, contributing to parasite clearance.
authors.affiliation: Laboratório de Pesquisa em Parasitologia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Camila Braz
authors.initials: CB
authors.lastname: Menezes
authors.affiliation: Laboratório de Pesquisa em Parasitologia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Graziela Vargas
authors.initials: GV
authors.lastname: Rigo
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Henrique
authors.initials: H
authors.lastname: Bridi
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Departamento de Ciências Básicas da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Danielle da Silva
authors.initials: DDS
authors.lastname: Trentin
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Faculdade de Farmácia e Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Alexandre José
authors.initials: AJ
authors.lastname: Macedo
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Gilsane Lino
authors.initials: GL
authors.lastname: von Poser
authors.affiliation: Laboratório de Pesquisa em Parasitologia, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Tiana
authors.identifier: http://orcid.org/0000-0002-8334-5105
authors.initials: T
authors.lastname: Tasca
mesh_terms: D000977:Antiparasitic Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D005260:Female; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D020902:Hypericum / Q000737:chemistry; D009711:Nucleotides / Q000378:metabolism; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D014247:Trichomonas Vaginitis / Q000188:drug therapy* / Q000469:parasitology; D014246:Trichomonas vaginalis / Q000187:drug effects* / Q000502:physiology
chemical_list: D000977:Antiparasitic Agents; D009711:Nucleotides; C000611093:isoaustrobrasilol B; D010696:Phloroglucinol
keywords: 
  Trichomonas vaginalis
  ; IL-8; isoaustrobrasilol B; neutrophils; phloroglucinol derivatives