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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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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. |
format | Online Article Text |
id | pubmed-6099706 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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