Tetrahydrophthalazinone Inhibitor of Phosphodiesterase with In Vitro Activity against Intracellular Trypanosomatids-Reference-Cited by-同舟云学术

Tetrahydrophthalazinone Inhibitor of Phosphodiesterase with In Vitro Activity against Intracellular Trypanosomatids

Published:2021-02-17 Issue:3 Volume:65 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

de Araújo Julianna Siciliano¹,Peres Raiza Brandão¹,Bernardino da Silva Patrícia¹,Batista Marcos Meuser¹,Sterk Geert Jan²,Maes Louis³,Caljon Guy³^ORCID,Leurs Rob²,de Koning Harry P.⁴,Kalejaiye Titilola D.⁴,Soeiro Maria de Nazaré Correia¹^ORCID

Affiliation:

1. Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

2. Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

3. Laboratory for Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Antwerp, Belgium

4. Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, United Kingdom

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 [EC 50 ], 6.6 to 39.5 μM). Increased cAMP levels of T. cruzi and its combination with benznidazole gave synergistic interaction.

Funder

MCTI | Conselho Nacional de Desenvolvimento Científico e Tecnológico

Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro

FP7 Ideas: European Research Council

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.00960-20

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