Author | Bonardi, Alessandro | |
Author | Vermelho, Alane Beatriz | |
Author | Cardoso, Veronica da Silva | |
Author | Pereira, Mirian Claudia de Souza | |
Author | Lara, Leonardo da Silva | |
Author | Selleri, Silvia | |
Author | Gratteri, Paola | |
Author | Supuran, Claudiu T. | |
Author | Nocentini, Alessio | |
Access date | 2019-09-17T11:13:49Z | |
Available date | 2019-09-17T11:13:49Z | |
Document date | 2019 | |
Citation | BONARDI, Alessandro et al. N‑Nitrosulfonamides as Carbonic Anhydrase Inhibitors: A Promising Chemotype for Targeting Chagas Disease and Leishmaniasis. ACS Medicinal Chemistry Letters, v. 10, p. 413-418, 2019. | pt_BR |
ISSN | 1948-5875 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/35620 | |
Language | eng | pt_BR |
Publisher | American Chemical Society | pt_BR |
Rights | restricted access | pt_BR |
Subject in Portuguese | Doença de Chagas | pt_BR |
Subject in Portuguese | Trypanosoma cruzi | pt_BR |
Subject in Portuguese | Leishmania | pt_BR |
Subject in Portuguese | Anidrase carbônica | pt_BR |
Subject in Portuguese | Grupo de ligação de zinco | pt_BR |
Subject in Portuguese | Inibição | pt_BR |
Subject in Portuguese | Antiparasitário | pt_BR |
Subject in Portuguese | Prata | pt_BR |
Title | N-Nitrosulfonamides as Carbonic Anhydrase Inhibitors: A Promising Chemotype for Targeting Chagas Disease and Leishmaniasis | pt_BR |
Type | Article | pt_BR |
DOI | 10.1021/acsmedchemlett.8b00430 | |
Abstract | Trypanosoma cruzi and Leishmania spp. are protozoa of the Trypanosomatidae family, respectively, responsible of the neglected tropical disorders (NTDs) Chagas disease and leishmaniasis. The present pharmacotherapy is often ineffective and exhibits serious side effects. The metalloenzyme carbonic anhydrases (CAs, EC 4.2.1.1) recently identified in these protozoans (α-TcCA and β-LdcCA) are novel promising targets for chemotherapeutic interventions. Herein, we report a series of N-nitrosulfonamides, as a novel chemotype to yield the target CA isoform selective inhibition over ubiquitous human isozymes. Two derivatives selected among the most active and selective ones for TcCA/LdcCA over off-target CAs were progressed as silver salts to in vitro studies with various developmental forms and spp of Trypanosoma cruzi and leishmania. Excellent values of parasites growth inhibition (IC50) were observed, with some selectivity index (over cytotoxicity for macrophages and Vero cells) being comparable or better than reference drugs. These findings make N-nitrosulfonamides and their salts promising lead compounds for a rational optimization of innovative agents for the treatment of Chagas disease and leishmaniasis based on CA inhibition. | pt_BR |
Affilliation | University of Florence. Department of NEUROFARBA, Pharmaceutical and Nutraceutical Section. Sesto Fiorentino. Firenze, Italy / University of Florence. Department of NEUROFARBA, Pharmaceutical and Nutraceutical Section. Laboratory of Molecular Modelling Cheminformatics & QSAR. Sesto Fiorentino, Italy. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. BIOINOVAR - Laboratórios de Biotecnologia: Biocatálise, Bioprodutos e Bioenergia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | University of Florence. Department of NEUROFARBA, Pharmaceutical and Nutraceutical Section. Laboratory of Molecular Modelling Cheminformatics & QSAR. Sesto Fiorentino, Italy. | pt_BR |
Affilliation | University of Florence. Department of NEUROFARBA, Pharmaceutical and Nutraceutical Section. Laboratory of Molecular Modelling Cheminformatics & QSAR. Sesto Fiorentino, Italy. | pt_BR |
Affilliation | University of Florence. Department of NEUROFARBA, Pharmaceutical and Nutraceutical Section. Sesto Fiorentino. Firenze, Italy. | pt_BR |
Affilliation | University of Florence. Department of NEUROFARBA, Pharmaceutical and Nutraceutical Section. Sesto Fiorentino. Firenze, Italy / University of Florence. Department of NEUROFARBA, Pharmaceutical and Nutraceutical Section. Laboratory of Molecular Modelling Cheminformatics & QSAR. Sesto Fiorentino, Italy. | pt_BR |
Subject | Chagas disease | pt_BR |
Subject | Trypanosoma cruzi | pt_BR |
Subject | Leishmania | pt_BR |
Subject | Carbonic anhydrase | pt_BR |
Subject | Zinc-binding group | pt_BR |
Subject | Inhibition | pt_BR |
Subject | Silver | pt_BR |
Subject | Antiparasitic | pt_BR |
e-ISSN | 1948-5875 | |
Embargo date | 2025-01-01 | |