The Efficacy of KG Series Derivatives for the Treatment of Toxoplasmosis.

摘要

Toxoplasma gondii is an intracellular parasite that has an alarming prevalence in the planet's human population. Currently, treatments exist for the acute infection but they carry poor host tolerance, and no cure exists for the latent infection. Chemical derivatives of previously published compounds demonstrating anti-Toxoplasma activity were generated to optimize their efficacy. The process of optimization outlined in this work involved a growth inhibition screen with two T. gondii strains and a battery of in vitro toxicity screens including mammalian cell line toxicity, metabolic stability with an S9 liver fraction, and mutagenicity with the Ames assay. The results of this work include 19 compounds with optimized potency against T. gondii and a characterized safety profile in a collection of mammalian cell lines and tissue mimics.