Phenotypic Screening of the MMV Global Health Priority Box Identifies Selective Compounds with Anti-Toxoplasma gondii Activity.

Toxoplasmosis remains a globally significant parasitic disease, with limited treatment options and reports of drug intolerance and inadequate efficacy, particularly against chronic stages. This study aimed to identify novel anti-Toxoplasma gondii compounds through the phenotypic screening of the Medicines for Malaria Venture (MMV) Global Health Priority Box (GHPB), a curated library of 240 chemically diverse molecules. Parasite viability and host cell cytotoxicity assays identified six lead compounds with the selectivity index (SI) exceeding 100, with MMV689404 (Triflumuron), MMV1794214 (Vaniliprole), and MMV1794211 showing SI >103, > 756, and >1000, respectively. In silico ADMET profiling revealed favorable pharmacokinetic and toxicity parameters for most hits, although Vaniliprole showed suboptimal gastrointestinal absorption and potential tumorigenicity. Comparative analysis with the existing literature confirmed previously reported antiparasitic activity for several compounds, reinforcing their relevance for repurposing. These findings highlight the potential of GHPB as a source of candidate molecules for further preclinical evaluation against toxoplasmosis.