Tetrahydrophthalazinone Inhibitor of Phosphodiesterase with In Vitro Activity against Intracellular Trypanosomatids.
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.
['de Araújo|Julianna Siciliano|JS|', 'Peres|Raiza Brandão|RB|', 'Bernardino da Silva|Patrícia|P|', 'Batista|Marcos Meuser|MM|', 'Sterk|Geert Jan|GJ|', 'Maes|Louis|L|', 'Caljon|Guy|G|0000-0002-4870-3202', 'Leurs|Rob|R|', 'de Koning|Harry P|HP|', 'Kalejaiye|Titilola D|TD|', 'Soeiro|Maria de Nazaré Correia|MNC|0000-0003-0078-6106']
D000981:Antiprotozoal Agents D014355:Chagas Disease D006801:Humans D007894:Leishmania mexicana D010727:Phosphoric Diester Hydrolases D014349:Trypanosoma cruzi
in vitro activity phosphodiesterase inhibitor T. cruzi cAMP L. amazonensis L. infantum