Screening for Inhibitors of Nuclear Import in Plasmodium falciparum and Toxoplasma gondii

Emerging drug resistance in Plasmodium species and Toxoplasma gondii threatens disease control worldwide, implying the urgent need for new therapeutic targets. We show for the first time that nuclear localization signal-dependent transport into the nucleus, mediated by importinα from P. falciparum and T. gondii, has promise as a target for small molecule inhibitors. We use AlphaScreen-based high-throughput screening to identify agents from LOPAC and pathogen box libraries to inhibit P. falciparum IMPα. Importantly, a number of the compounds inhibit the growth of both P. falciparum and T. gondii in culture, highlighting the utility of this approach for drug discovery against malaria and toxoplasmosis.