Concurrent Assessment of Synthetic and Natural Compounds on the Proliferation of <em>Toxoplasma gondii</em> in <em>In Vitro</em> Models

Concurrent evaluation of the antiparasitic efficacy of synthetic and natural compounds can provide novel insights into the development of anti-Toxoplasma drugs. We assessed 16 synthetic compounds and fractions derived from the leaves of two Tabebuia tree species for their in vitro activity against live parasites, employing strains that express green fluorescent protein and specific identification of bradyzoites with an anti-BAG1 monoclonal antibody. This study successfully identified several promising synthetic compounds with potent anti-Toxoplasma activity and favorable in vitro selectivity profiles, notably pyrazoline 2 and thiazolidinone 9. One thiazolidinone compound exhibited significant activity against extracellular tachyzoites, whereas one tree fraction demonstrated excellent activity against both tachyzoites and bradyzoites. Additionally, their in silico ADMET properties suggest their potential for good in vivo performance and CNS penetration. Although the natural extracts showed less potency in their crude form, they provide a basis for future purification efforts. The simultaneous evaluation of compounds sourced from diverse discovery pipelines can offer valuable insights into the development of drugs that target various biological pathways.