Article
Tetrahydrophthalazinone Inhibitor of Phosphodiesterase with In Vitro Activity against Intracellular Trypanosomatids
Registro en:
ARAÚJO, Juliana Siciliano de et al. Tetrahydrophthalazinone Inhibitor of Phosphodiesterase with In Vitro Activity against Intracellular Trypanosomatids. Antimicrobial Agents and Chemotherapy., v. 65, n. 3, e00960-20, 5 p, Feb. 2021.
1098-6596
10.1128/AAC.00960-20
Autor
Araújo, Julianna Siciliano de
Peres, Raiza Brandão
Silva, Patrícia Bernardino da
Batista, Marcos Meuser
Sterk, Geert Jan
Maes, Louis
Caljon, Guy
Leurs, Rob
Koning, Harry P. de
Kalejaiye, Titilola D.
Soeiro, Maria de Nazareth Correia
Resumen
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 39.5mM).
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.