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Anti-Mycobacterium tuberculosis Activity of Esters of Quinoxaline 1,4-Di-N-Oxide

Tuberculosis continues to be a public health problem in the world, and drug resistance has been a major obstacle in its treatment. Quinoxaline 1,4-di-N-oxide has been proposed as a scaffold to design new drugs to combat this disease. To examine the efficacy of this compound, this study evaluates met...

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Autores principales: Palos, Isidro, Luna-Herrera, Julieta, Lara-Ramírez, Edgar E., Loera-Piedra, Alejandra, Fernández-Ramírez, Emanuel, Aguilera-Arreola, Ma. Guadalupe, Paz-González, Alma D., Monge, Antonio, Wan, Baojie, Franzblau, Scott, Rivera, Gildardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099706/
https://www.ncbi.nlm.nih.gov/pubmed/29914062
http://dx.doi.org/10.3390/molecules23061453
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author Palos, Isidro
Luna-Herrera, Julieta
Lara-Ramírez, Edgar E.
Loera-Piedra, Alejandra
Fernández-Ramírez, Emanuel
Aguilera-Arreola, Ma. Guadalupe
Paz-González, Alma D.
Monge, Antonio
Wan, Baojie
Franzblau, Scott
Rivera, Gildardo
author_facet Palos, Isidro
Luna-Herrera, Julieta
Lara-Ramírez, Edgar E.
Loera-Piedra, Alejandra
Fernández-Ramírez, Emanuel
Aguilera-Arreola, Ma. Guadalupe
Paz-González, Alma D.
Monge, Antonio
Wan, Baojie
Franzblau, Scott
Rivera, Gildardo
author_sort Palos, Isidro
collection PubMed
description Tuberculosis continues to be a public health problem in the world, and drug resistance has been a major obstacle in its treatment. Quinoxaline 1,4-di-N-oxide has been proposed as a scaffold to design new drugs to combat this disease. To examine the efficacy of this compound, this study evaluates methyl, ethyl, isopropyl, and n-propyl esters of quinoxaline 1,4-di-N-oxide derivatives in vitro against Mycobacterium tuberculosis (pansusceptible and monoresistant strains). Additionally, the inhibitory effect of esters of quinoxaline 1,4-di-N-oxide on M. tuberculosis gyrase supercoiling was examined, and a stability analysis by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS) was also carried out. Results showed that eight compounds (T-007, T-018, T-011, T-069, T-070, T-072, T-085 and T-088) had an activity similar to that of the reference drug isoniazid (minimum inhibitory concentration (MIC) = 0.12 µg/mL) with an effect on nonreplicative cells and drug monoresistant strains. Structural activity relationship analysis showed that the steric effect of an ester group at 7-position is key to enhancing its biological effects. Additionally, T-069 showed a high stability after 24 h in human plasma at 37 °C.
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spelling pubmed-60997062018-11-13 Anti-Mycobacterium tuberculosis Activity of Esters of Quinoxaline 1,4-Di-N-Oxide Palos, Isidro Luna-Herrera, Julieta Lara-Ramírez, Edgar E. Loera-Piedra, Alejandra Fernández-Ramírez, Emanuel Aguilera-Arreola, Ma. Guadalupe Paz-González, Alma D. Monge, Antonio Wan, Baojie Franzblau, Scott Rivera, Gildardo Molecules Article Tuberculosis continues to be a public health problem in the world, and drug resistance has been a major obstacle in its treatment. Quinoxaline 1,4-di-N-oxide has been proposed as a scaffold to design new drugs to combat this disease. To examine the efficacy of this compound, this study evaluates methyl, ethyl, isopropyl, and n-propyl esters of quinoxaline 1,4-di-N-oxide derivatives in vitro against Mycobacterium tuberculosis (pansusceptible and monoresistant strains). Additionally, the inhibitory effect of esters of quinoxaline 1,4-di-N-oxide on M. tuberculosis gyrase supercoiling was examined, and a stability analysis by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS) was also carried out. Results showed that eight compounds (T-007, T-018, T-011, T-069, T-070, T-072, T-085 and T-088) had an activity similar to that of the reference drug isoniazid (minimum inhibitory concentration (MIC) = 0.12 µg/mL) with an effect on nonreplicative cells and drug monoresistant strains. Structural activity relationship analysis showed that the steric effect of an ester group at 7-position is key to enhancing its biological effects. Additionally, T-069 showed a high stability after 24 h in human plasma at 37 °C. MDPI 2018-06-15 /pmc/articles/PMC6099706/ /pubmed/29914062 http://dx.doi.org/10.3390/molecules23061453 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Palos, Isidro
Luna-Herrera, Julieta
Lara-Ramírez, Edgar E.
Loera-Piedra, Alejandra
Fernández-Ramírez, Emanuel
Aguilera-Arreola, Ma. Guadalupe
Paz-González, Alma D.
Monge, Antonio
Wan, Baojie
Franzblau, Scott
Rivera, Gildardo
Anti-Mycobacterium tuberculosis Activity of Esters of Quinoxaline 1,4-Di-N-Oxide
title Anti-Mycobacterium tuberculosis Activity of Esters of Quinoxaline 1,4-Di-N-Oxide
title_full Anti-Mycobacterium tuberculosis Activity of Esters of Quinoxaline 1,4-Di-N-Oxide
title_fullStr Anti-Mycobacterium tuberculosis Activity of Esters of Quinoxaline 1,4-Di-N-Oxide
title_full_unstemmed Anti-Mycobacterium tuberculosis Activity of Esters of Quinoxaline 1,4-Di-N-Oxide
title_short Anti-Mycobacterium tuberculosis Activity of Esters of Quinoxaline 1,4-Di-N-Oxide
title_sort anti-mycobacterium tuberculosis activity of esters of quinoxaline 1,4-di-n-oxide
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099706/
https://www.ncbi.nlm.nih.gov/pubmed/29914062
http://dx.doi.org/10.3390/molecules23061453
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