Kongkasuriyachai D.Koompapong K.Tuyapala N.Hoarau M.Jantra T.Pengon J.Talawanich Y.Tanasugarn L.Decharuangsilp S.Arwon U.Vanichtanankul J.Yuthavong Y.Kamchonwongpaisan S.Mahittikorn A.Mahidol University2026-04-112026-04-112026-06-01Infection Genetics and Evolution Vol.140 (2026)15671348https://repository.li.mahidol.ac.th/handle/123456789/116139Toxoplasmosis remains a threat for neonates and immuno-compromised populations, against which only broad spectrum antiparasitic drugs are currently available. Here, a virtual screen was conducted on a Plasmodium falciparum dihydrofolate reductase (DHFR) inhibitor library to identify novel Toxoplasma gondii DHFR inhibitors. Three hit compounds were identified, showing nM-range in vitro activity against T. gondii and high selectivity compared to mammalian cells. All compounds are highly lipophilic. However, the most promising compounds, P12 and P33, did not exhibit significantly lower parasite burden of RH-T. gondii from infected mice in a 4-day suppressive test. Although P33-treated mice appeared to have longer median survival time compared to vehicle control group, the survival time was still shorter than the survival time in the pyrimethamine-treated group. Nonetheless, the promising activity of our compounds can guide further anti-toxoplasmosis drug development.Biochemistry, Genetics and Molecular BiologyAgricultural and Biological SciencesMedicineImmunology and MicrobiologyArticleSCOPUS10.1016/j.meegid.2026.1059352-s2.0-1050347642291567725741912015