In vitro evaluation of [beta]-carboline alkaloids as potential anti-Toxoplasma agents

Toxoplasmosis is a worldwide infection caused by the protozoan parasite Toxoplasma gondii, which causes chorioretinitis and neurological defects in congenitally infected newborns or immunodeficient patients. The efficacy of the current treatment is limited, primarily by serious host toxicity. In rec...

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Bibliographic Details
Published in:BMC research notes 2013-05, Vol.6 (1), p.193-193
Main Authors: Alomar, Maria L, Rasse-Suriani, Federico AO, Ganuza, Agustina, Cóceres, Verónica M, Cabrerizo, Franco M, Angel, Sergio O
Format: Article
Language:English
Subjects:
Alkaloids
Analysis
Aqueous solutions
Cell culture
Cell cycle
Cyclin-dependent kinases
Deoxyribonucleic acid
Dihydrofolate reductase
DNA
Drug dosages
Drug resistance
Parasites
Physiological aspects
Studies
Toxoplasma
Toxoplasma gondii
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Summary:Toxoplasmosis is a worldwide infection caused by the protozoan parasite Toxoplasma gondii, which causes chorioretinitis and neurological defects in congenitally infected newborns or immunodeficient patients. The efficacy of the current treatment is limited, primarily by serious host toxicity. In recent years, research has focused on the development of new drugs against T. gondii. [beta]-Carbolines ([beta]Cs), such as harmane, norharmane and harmine, are a group of naturally occurring alkaloids that show microbicidal activity. In this work, harmane, norharmane and harmine were tested against T. gondii. The treatment of extracellular tachyzoites with harmane, norharmane and harmine showed a 2.5 to 3.5-fold decrease in the invasion rates at doses of 40 [mu]M (harmane and harmine) and 2.5 [mu]M (norharmane) compared with the untreated parasites. Furthermore, an effect on the replication rate could also be observed with a decrease of 1 (harmane) and 2 (norharmane and harmine) division rounds at doses of 5 to 12.5 [mu]M. In addition, the treated parasites presented either delayed or no monolayer lysis compared with the untreated parasites. The three [beta]C alkaloids studied (norharmane, harmane and harmine) exhibit anti-T. gondii effects as evidenced by the partial inhibition of parasite invasion and replication. A dose-response effect was observed at a relatively low drug concentration (< 40 [mu]M), at which no cytotoxic effect was observed on the host cell line (Vero).
ISSN:1756-0500
1756-0500
DOI:10.1186/1756-0500-6-193