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

## TL;DR

This study screens a collection of 240 diverse compounds to find new treatments for toxoplasmosis, a parasitic disease with limited current therapies.

## Contribution

The study identifies six selective anti-Toxoplasma gondii compounds from the MMV Global Health Priority Box with high selectivity indices.

## Key findings

- Three compounds (MMV689404, MMV1794214, MMV1794211) showed selectivity indices exceeding 100, with the highest over 1000.
- In silico ADMET profiling showed favorable pharmacokinetic and toxicity profiles for most compounds.
- Several compounds had previously reported antiparasitic activity, supporting their potential for drug repurposing.

## Abstract

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.