In Vitro and In Silico Analysis of New n-Butyl and Isobutyl Quinoxaline-7-carboxylate 1,4-di-<i>N</i>-oxide Derivatives against <i>Trypanosoma cruzi</i> as Trypanothione Reductase Inhibitors

In Vitro and In Silico Analysis of New n-Butyl and Isobutyl Quinoxaline-7-carboxylate 1,4-di-<i>N</i>-oxide Derivatives against <i>Trypanosoma cruzi</i> as Trypanothione Reductase Inhibitors

American trypanosomiasis is a worldwide health problem that requires attention due to ineffective treatment options. We evaluated n-butyl and isobutyl quinoxaline-7-carboxylate 1,4-di-<i>N</i>-oxide derivatives against trypomastigotes of the <i>Trypanosoma cruzi</i> strains N...

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Bibliographic Details
Main Authors: Alonzo González-González, Oscar Sánchez-Sánchez, R. Luise Krauth-Siegel, Maria Laura Bolognesi, Rogelio Gớmez-Escobedo, Benjamín Nogueda-Torres, Lenci K. Vázquez-Jiménez, Emma Saavedra, Rusely Encalada, José Carlos Espinoza-Hicks, Alma D. Paz-González, Gildardo Rivera
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:International Journal of Molecular Sciences
Subjects:
Chagas disease
trypanothione reductase
chemical synthesis
trypomastigotes
quinoxaline-1,4-di-<i>N</i>-oxide
Online Access:https://www.mdpi.com/1422-0067/23/21/13315
Description
Summary:American trypanosomiasis is a worldwide health problem that requires attention due to ineffective treatment options. We evaluated n-butyl and isobutyl quinoxaline-7-carboxylate 1,4-di-<i>N</i>-oxide derivatives against trypomastigotes of the <i>Trypanosoma cruzi</i> strains NINOA and INC-5. An in silico analysis of the interactions of 1,4-di-<i>N</i>-oxide on the active site of trypanothione reductase (TR) and an enzyme inhibition study was carried out. The n-butyl series compound identified as T-150 had the best trypanocidal activity against <i>T. cruzi</i> trypomastigotes, with a 13% TR inhibition at 44 μM. The derivative T-147 behaved as a mixed inhibitor with Ki and Ki’ inhibition constants of 11.4 and 60.8 µM, respectively. This finding is comparable to the TR inhibitor mepacrine (Ki = 19 µM).
ISSN:1661-6596
1422-0067

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