Next Article in Journal
Phosphoproteomics of Retinoblastoma: A Pilot Study Identifies Aberrant Kinases
Previous Article in Journal
Anticoagulant Activities of Indobufen, an Antiplatelet Drug
Article Menu
Issue 6 (June) cover image

Export Article

Open AccessArticle
Molecules 2018, 23(6), 1453; https://doi.org/10.3390/molecules23061453

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

1
Unidad Académica Multidisciplinaria Reynosa-Rodhe, Universidad Autónoma de Tamaulipas, Carr. Reynosa-San Fernando, s/n, Reynosa 88779, Mexico
2
Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, Mexico
3
Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social (IMSS), Alameda Trinidad García de la Cadena, s/n, Zacatecas 98000, Mexico
4
Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, Mexico
5
Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Boulevard del Maestro, s/n, Esq. Elías Piña, Reynosa 88710, Mexico
6
Unidad de Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiología Aplicada (CIFA), Universidad de Navarra, C/Irunlarrea s/n, 31080 Pamplona, Spain
7
Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood St., Chicago, IL 60612, USA
*
Author to whom correspondence should be addressed.
Received: 15 May 2018 / Revised: 5 June 2018 / Accepted: 13 June 2018 / Published: 15 June 2018
(This article belongs to the Section Medicinal Chemistry)
Full-Text   |   PDF [2612 KB, uploaded 21 June 2018]   |  

Abstract

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. View Full-Text
Keywords: esters; quinoxaline 1,4-di-N-oxide; Mycobacterium tuberculosis; DNA gyrase; drug resistance esters; quinoxaline 1,4-di-N-oxide; Mycobacterium tuberculosis; DNA gyrase; drug resistance
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Palos, I.; Luna-Herrera, J.; Lara-Ramírez, E.E.; Loera-Piedra, A.; Fernández-Ramírez, E.; Aguilera-Arreola, M.G.; Paz-González, A.D.; Monge, A.; Wan, B.; Franzblau, S.; Rivera, G. Anti-Mycobacterium tuberculosis Activity of Esters of Quinoxaline 1,4-Di-N-Oxide. Molecules 2018, 23, 1453.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top