Please use this identifier to cite or link to this item:
https://www.arca.fiocruz.br/handle/icict/35620
Type
ArticleCopyright
Restricted access
Embargo date
2025-01-01
Collections
- IOC - Artigos de Periódicos [12488]
Metadata
Show full item record
N-NITROSULFONAMIDES AS CARBONIC ANHYDRASE INHIBITORS: A PROMISING CHEMOTYPE FOR TARGETING CHAGAS DISEASE AND LEISHMANIASIS
Trypanosoma cruzi
Leishmania
Anidrase carbônica
Grupo de ligação de zinco
Inibição
Antiparasitário
Prata
Trypanosoma cruzi
Leishmania
Carbonic anhydrase
Zinc-binding group
Inhibition
Silver
Antiparasitic
Author
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.
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.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.
University of Florence. Department of NEUROFARBA, Pharmaceutical and Nutraceutical Section. Laboratory of Molecular Modelling Cheminformatics & QSAR. Sesto Fiorentino, Italy.
University of Florence. Department of NEUROFARBA, Pharmaceutical and Nutraceutical Section. Laboratory of Molecular Modelling Cheminformatics & QSAR. Sesto Fiorentino, Italy.
University of Florence. Department of NEUROFARBA, Pharmaceutical and Nutraceutical Section. Sesto Fiorentino. Firenze, Italy.
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.
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.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.
University of Florence. Department of NEUROFARBA, Pharmaceutical and Nutraceutical Section. Laboratory of Molecular Modelling Cheminformatics & QSAR. Sesto Fiorentino, Italy.
University of Florence. Department of NEUROFARBA, Pharmaceutical and Nutraceutical Section. Laboratory of Molecular Modelling Cheminformatics & QSAR. Sesto Fiorentino, Italy.
University of Florence. Department of NEUROFARBA, Pharmaceutical and Nutraceutical Section. Sesto Fiorentino. Firenze, Italy.
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.
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.
Keywords in Portuguese
Doença de ChagasTrypanosoma cruzi
Leishmania
Anidrase carbônica
Grupo de ligação de zinco
Inibição
Antiparasitário
Prata
Keywords
Chagas diseaseTrypanosoma cruzi
Leishmania
Carbonic anhydrase
Zinc-binding group
Inhibition
Silver
Antiparasitic
Share