Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/17769
Title: Hydroxamic acid derivatives: a promising scaffold for rational compound optimization in Chagas disease
Authors: Menezes, Dayanne da Rocha de
Calvet, Claudia Magalhães
Rodrigues, Giseli Capaci
Pereira, Mirian Claudia de Souza
Almeida, Igor Rodrigues
Aguiar, Alcino Palermo de
Supuran, Claudiu T.
Vermelho, Alane Beatriz
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 / Faculdade São Francisco de Barreiras (FASB). Barreiras, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultra-estrutura Celular. Rio de Janeiro, RJ. Brasil.
Universidade do Grande Rio. Escola de Ciência e Tecnologia. Programa de Pós-Graduação em Ensino das Ciências. Duque de Caxias, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultra-estrutura Celular. Rio de Janeiro, RJ. Brasil.
Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Departamento de Produtos Naturais e Alimentos. Rio de Janeiro, RJ, Brasil.
Instituto Militar de Engenharia. Departamento de Química. Laboratório de Síntese Orgãnica. Rio de Janeiro, RJ, Brasil.
Universitá degli Studi di Firenzi. Polo Scientifico. Laboratorio di Chimica Bioinorganica. Sesto Fiorentino (Florence), 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.
Abstract: This work describes the antitrypanocidal activity of two hydroxamic acid derivatives containing o-ethoxy (HAD1) and p-ethoxy (HAD2) as substituent in the aromatic ring linked to the isoxazoline ring. HAD1 and HAD2 induced a significant reduction in the number of intracellular parasites and consequently showed activity on the multiplication of the parasite. Treatment of cardiomyocytes and macrophages with the compounds revealed no significant loss in cell viability. Ultrastructural alterations after treatment of cardiomyocytes or macrophages infected by Trypanosoma cruzi with the IC50 value of HAD1 revealed alterations to amastigotes, showing initial damage seen as swelling of the kinetoplast. This gave a good indication of the ability of the drug to permeate through the host cell membrane as well as its selectivity to the parasite target. Both compounds HAD1 and 2 were able to reduce the cysteine peptidases and decrease the activity of metallopeptidases.
Keywords: Chagas disease
hydroxamic acid derivatives
Trypanosoma cruzi
keywords: Trypanosoma cruzi
Doença de Chagas
Derivados de ácido hidroxâmico
Issue Date: 2016
Publisher: Taylor & Francis
Citation: MENEZES, Dayanne da Rocha de; et al. Hydroxamic acid derivatives: a promising scaffold for rational compound optimization in Chagas disease. Journal of Enzyme Inhibition and Medicinal Chemistry, v.31, n.6, p.964-973, 2016.
DOI: 10.3109/14756366.2015.1077330
ISSN: 1475-6366
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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