Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/48928

Type
Article
Copyright
Open access
Collections
Share

Statistics
Metadata
Show full item record

TETRAHYDROPHTHALAZINONE INHIBITOR OF PHOSPHODIESTERASE WITH IN VITRO ACTIVITY AGAINST INTRACELLULAR TRYPANOSOMATIDS
Araújo, Julianna Siciliano de et al. | Date Issued: 2021
Author
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
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam. Amsterdam, The Netherlands.
Laboratory for Microbiology, Parasitology and Hygiene (LMPH). University of Antwerp. Antwerp, Belgium.
Laboratory for Microbiology, Parasitology and Hygiene (LMPH). University of Antwerp. Antwerp, Belgium.
Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam. Amsterdam, The Netherlands.
Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary & Life Sciences. University of Glasgow. Glasgow, United Kingdom.
Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary & Life Sciences. University of Glasgow. Glasgow, United Kingdom.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Biologia Celular. Rio de Janeiro, RJ, Brasil.
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.
Keywords in Portuguese
Trypanosoma cruzi
Inibidor de fosfodiesterase
Atividade in vitro
 
Keywords
L. amazonensis
L. infantum
T. cruzi
cAMP
in vitro activity
Phosphodiesterase inhibitor
 
Publisher
American Society for Microbiology
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.
DOI
10.1128/AAC.00960-20
ISSN
1098-6596