Structure-activity relationships of cytochrome inhibitors.

INTRODUCTION

is a prolific apicomplexan parasite that infects human and nonhuman animals worldwide and can cause severe brain and eye disease. Safer, more effective therapies for toxoplasmosis are needed. Cytochrome inhibitors are remarkably effective against toxoplasmosis and other apicomplexan-caused diseases.

AREAS COVERED

This work reviews cytochrome inhibitors. Emphasis is placed on the structure-activity relationships of these inhibitors with regard to efficacy, pharmacokinetics, selectivity of cytochrome over host, safety, and potential therapeutic strategies.

EXPERT OPINION

Cytochrome inhibitors are highly promising compounds for toxoplasmosis that have been effective in clinical and preclinical studies. Clinical experience with atovaquone previously validated cytochrome as a tractable drug target and, over the past decade, optimization of cytochrome inhibitors has resulted in improved bioavailability, metabolic stability, potency, blood-brain barrier penetration, and selectivity for the cytochrome over the mammalian . Recent studies have demonstrated preclinical safety, identified novel therapeutic strategies for toxoplasmosis using synergistic combinations or long-acting administration and provided insight into their role in chronic infection. This research has identified drug candidates that are more effective than clinically used drugs in preclinical measures of efficacy.