Tetrahydrophthalazinone Inhibitor of Phosphodiesterase with In Vitro Activity against Intracellular Trypanosomatids.
Julianna Siciliano de AraújoRaiza Brandão PeresPatrícia Bernardino da SilvaMarcos Meuser BatistaGeert Jan SterkLouis MaesGuy CaljonRob LeursHarry P de KoningTitilola D KalejaiyeMaria de Nazaré Correia SoeiroPublished in: Antimicrobial agents and chemotherapy (2021)
The phosphodiesterase inhibitor tetrahydrophthalazinone NPD-008 was explored by phenotypic in vitro screening, target validation, and ultrastructural approaches against Trypanosoma cruzi NPD-008 displayed activity against different forms and strains of T. cruzi (50% effective concentration [EC50], 6.6 to 39.5 μM). NPD-008 increased cAMP levels of T. cruzi and its combination with benznidazole gave synergistic interaction. It was also moderately active against intracellular amastigotes of Leishmania amazonensis and Leishmania infantum, confirming a potential activity profile as an antitrypanosomatid drug candidate.