title: A new type of pterocarpanquinone that affects Toxoplasma gondii tachyzoites in vitro.
abstract: Toxoplasma gondii, the agent of Toxoplasmosis, is an obligate intracellular protozoan able to infect a wide range of vertebrate cells, including nonprofessional and professional phagocytes. Therefore, drugs must have intracellular activities in order to control this parasite. The most common therapy for Toxoplasmosis is the combination of sulfadiazine and pyrimethamine. This treatment is associated with adverse reactions, thus, the development of new drugs is necessary. In previous studies, naphthoquinone derivatives showed anti-cancer activity functioning as agents capable of acting on groups of DNA, preventing cancer cells duplication. These derivatives also display anti-parasitic activity against Plasmodium falciparum and Leishmania amazonensis. The derivative pterocarpanquinone tested in this work resulted from the molecular hybridization between pterocarpans and naphtoquinone that presents anti-tumoral and anti-parasitic activities of lapachol. The aim of this work was to determine if this derivative is able to change T. gondii growth within LLC-MK2 cells. The drug did not arrest host cell growth, but was able to decrease the infection index of T. gondii with an IC(50) of 2.5 μM. Scanning and transmission electron microscopy analysis showed morphological changes of parasites including membrane damage. The parasite that survived tended to encyst as seen by Dolichos biflorus lectin staining and Bag-1 expression. These results suggest that pterocarpanquinones are drugs potentially important for the killing and encystment of T. gondii.
authors.affiliation: Laboratório de Tecnologia em Cultura de Células, Centro Universitário Estadual da Zona Oeste (UEZO) - Av. Manuel Caldeira de Alvarenga, 1203, Campo Grande, Rio de Janeiro, RJ, CEP: 23070-200, Brazil. julianaportes@yahoo.com.br
authors.forename: Juliana de Araujo
authors.initials: Jde A
authors.lastname: Portes
authors.forename: Chaquip Daher
authors.initials: CD
authors.lastname: Netto
authors.forename: Alcides José Monteiro
authors.initials: AJ
authors.lastname: da Silva
authors.forename: Paulo Roberto Ribeiro
authors.initials: PR
authors.lastname: Costa
authors.forename: Renato Augusto
authors.initials: RA
authors.lastname: DaMatta
authors.forename: Thiago Alves Teixeira
authors.initials: TA
authors.lastname: dos Santos
authors.forename: Wanderley
authors.initials: W
authors.lastname: De Souza
authors.forename: Sergio Henrique
authors.initials: SH
authors.lastname: Seabra
mesh_terms: D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000469:parasitology; D008253:Macaca mulatta; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D036343:Pterocarpans / Q000737:chemistry / Q000494:pharmacology*; D014122:Toxoplasma / Q000187:drug effects* / Q000648:ultrastructure
chemical_list: D036343:Pterocarpans