title: New naphthoquinones and an alkaloid with in vitro activity against Toxoplasma gondii RH and EGS strains.
abstract: The efficacy of three amino-terpenyl naphthoquinones and the alkaloid liriodenine were examined against tachyzoites and tissues cysts of the RH and EGS strains, respectively. Monolayers of 2C4 fibroblasts infected with tachyzoites of the RH strain were incubated with different concentrations of the compounds for 48 h. Specifically, 7-(4-methyl-3-pentenyl)-2-pyrrolidine-[1,4]-naphthoquinone (QUI-5), 6-(4-methyl-3-pentenyl)-2-pyrrolidine-[1,4]-naphthoquinone (QUI-6), 6-(4-methylpentyl)-2-pyrrolidine-[1,4]-naphthoquinone (QUI-11), and 8 h-benzo[g]-1,3-benzodioxolo[6,5,4-de]quinolin-8-one,9Cl-1,2-methylene dioxiaporfina (liriodenine) inhibited intracellular replication of T. gondii. The IC(50) values obtained for compounds QUI-5 and QUI-6 were 69.35 and 172.81 μM (i.e., 21.4 and 53.4 μg/mL), respectively. The naphthoquinone QUI-11 and liriodenine significantly inhibited intracellular replication of T. gondii. The IC(50) values obtained with these experiments were 0.32 and 0.07 μM (i.e., 0.1 and 0.02 μg/mL), respectively. Compounds QUI-5, QUI-6, QUI-11 and liriodenine demonstrated lower toxicity for 2C4 fibroblasts compared to atovaquone. In addition, cysts isolated from the brains of mice chronically infected with the EGS strain were exposed to the compounds. Infectivity of the cysts after incubation with the compounds was assessed by infection of mice. The data obtained showed that in vitro incubation with QUI-6, QUI-11 and liriodenine inhibited the infectivity of the bradyzoites. This activity was time- and concentration-dependent.
authors.affiliation: Laboratório de Microscopia, Instituto de Ciências Agrárias, Faculdade de Estudos Administrativos, FEAD, Brazil.
authors.forename: Ronize Andréia
authors.initials: RA
authors.lastname: Ferreira
authors.forename: Alaide Braga
authors.initials: AB
authors.lastname: de Oliveira
authors.forename: Simone Andrade
authors.initials: SA
authors.lastname: Gualberto
authors.forename: José M
authors.initials: JM
authors.lastname: Miguel Del Corral
authors.forename: Ricardo Toshio
authors.initials: RT
authors.lastname: Fujiwara
authors.forename: Pedro Henrique
authors.initials: PH
authors.lastname: Gazzinelli Guimarães
authors.forename: Ricardo Wagner
authors.initials: RW
authors.lastname: de Almeida Vitor
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology; D001060:Aporphines / Q000737:chemistry / Q000494:pharmacology*; D053626:Atovaquone / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D003049:Coccidiostats / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000469:parasitology*; D052816:Foreskin / Q000166:cytology; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013411:Sulfadiazine / Q000737:chemistry / Q000494:pharmacology; D014122:Toxoplasma / Q000187:drug effects* / Q000472:pathogenicity; D014124:Toxoplasmosis, Animal / Q000188:drug therapy / Q000469:parasitology
chemical_list: D000962:Antimalarials; D001060:Aporphines; D003049:Coccidiostats; D009285:Naphthoquinones; D013411:Sulfadiazine; C026980:liriodenine; D053626:Atovaquone