Author | Araújo, Julianna Siciliano de | |
Author | Peres, Raiza Brandão | |
Author | Silva, Patrícia Bernardino da | |
Author | Batista, Marcos Meuser | |
Author | Sterk, Geert Jan | |
Author | Maes, Louis | |
Author | Caljon, Guy | |
Author | Leurs, Rob | |
Author | Koning, Harry P. de | |
Author | Kalejaiye, Titilola D. | |
Author | Soeiro, Maria de Nazareth Correia | |
Access date | 2021-09-03T12:59:29Z | |
Available date | 2021-09-03T12:59:29Z | |
Document date | 2021 | |
Citation | 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. | pt_BR |
ISSN | 1098-6596 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/48928 | |
Language | eng | pt_BR |
Publisher | American Society for Microbiology | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Trypanosoma cruzi | pt_BR |
Subject in Portuguese | Inibidor de fosfodiesterase | pt_BR |
Subject in Portuguese | Atividade in vitro | pt_BR |
Title | Tetrahydrophthalazinone Inhibitor of Phosphodiesterase with In Vitro Activity against Intracellular Trypanosomatids | pt_BR |
Type | Article | pt_BR |
DOI | 10.1128/AAC.00960-20 | |
Abstract | 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. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam. Amsterdam, The Netherlands. | pt_BR |
Affilliation | Laboratory for Microbiology, Parasitology and Hygiene (LMPH). University of Antwerp. Antwerp, Belgium. | pt_BR |
Affilliation | Laboratory for Microbiology, Parasitology and Hygiene (LMPH). University of Antwerp. Antwerp, Belgium. | pt_BR |
Affilliation | Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam. Amsterdam, The Netherlands. | pt_BR |
Affilliation | Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary & Life Sciences. University of Glasgow. Glasgow, United Kingdom. | pt_BR |
Affilliation | Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary & Life Sciences. University of Glasgow. Glasgow, United Kingdom. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | L. amazonensis | pt_BR |
Subject | L. infantum | pt_BR |
Subject | T. cruzi | pt_BR |
Subject | cAMP | pt_BR |
Subject | in vitro activity | pt_BR |
Subject | Phosphodiesterase inhibitor | pt_BR |