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.