A tetrahydrophthalazinone inhibitor of phosphodiesterase with in vitro activity against intracellular trypanosomatids

de Araújo, J. S. et al. (2021) A tetrahydrophthalazinone inhibitor of phosphodiesterase with in vitro activity against intracellular trypanosomatids. Antimicrobial Agents and Chemotherapy, 65(3), e00960-20. (doi: 10.1128/AAC.00960-20) (PMID:33361300) (PMCID:PMC8092546)

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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.

Item Type:Articles
Additional Information:This study was supported by grants from Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação Oswaldo Cruz, and PAEF/CNPq/Fiocruz. The PDE4NPD project was supported by the European Union 7th Framework Program (FP7/2007-2013) under grant agreement no. 602666. M.D.N.C.S. is a research fellow of CNPq and CNE research.
Glasgow Author(s) Enlighten ID:De Koning, Professor Harry and Kalejaiye, Miss Titilola
Authors: de Araújo, J. S., Peres, R. B., Bernardino da Silva, P., Batista, M. M., Sterk, G. J., Maes, L., Caljon, G., Leurs, R., De Koning, H. P., Kalejaiye, T. D., and Soeiro, M. d. N. C.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Antimicrobial Agents and Chemotherapy
Publisher:American Society for Microbiology
ISSN (Online):1098-6596
Published Online:23 December 2020

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
169936PDE4NTD: Phosphodieasease inhibitors for the treatment of Neglected Parasitic Diseases.Harry De KoningEuropean Commission (EC)602666III - Parasitology