Hydroxamic acid derivatives: a promising scaffold for rational compound optimization in Chagas disease

Journal of Enzyme Inhibition and Medicinal Chemistry
Dayanne da Rocha de MenezesAlane Beatriz Vermelho

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.

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Citations

Sep 13, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Sonia Del PreteClemente Capasso
Feb 6, 2017·Bioorganic & Medicinal Chemistry·Alane B VermelhoClaudiu T Supuran
Mar 22, 2018·Metabolites·Claudiu T Supuran
Dec 2, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Alane Beatriz VermelhoClaudiu T Supuran
Dec 28, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Alessio NocentiniJean-Yves Winum
Jun 21, 2019·Journal of Enzyme Inhibition and Medicinal Chemistry·Alessio NocentiniClaudiu T Supuran
May 1, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Verônica da Silva CardosoClaudiu T Supuran
Jun 12, 2019·International Journal of Molecular Sciences·Anacleto S de SouzaAdriano D Andricopulo
Apr 19, 2019·ACS Medicinal Chemistry Letters·Alessandro BonardiAlessio Nocentini
Jan 8, 2020·Journal of Agricultural and Food Chemistry·Rodrigo M FráguasDenilson F Oliveira
Feb 18, 2021·Current Pharmaceutical Design·Aline A Zuma, Wanderley de Souza

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