Cargando…
Potential Mechanism of Action of meso-Dihydroguaiaretic Acid on Mycobacterium tuberculosis H37Rv
The isolation and characterization of the lignan meso-dihydroguaiaretic acid (MDGA) from Larrea tridentata and its activity against Mycobacterial tuberculosis has been demonstrated, but no information regarding its mechanism of action has been documented. Therefore, in this study we carry out the ge...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271217/ https://www.ncbi.nlm.nih.gov/pubmed/25474289 http://dx.doi.org/10.3390/molecules191220170 |
_version_ | 1783376877439680512 |
---|---|
author | Clemente-Soto, Aldo F. Balderas-Rentería, Isaías Rivera, Gildardo Segura-Cabrera, Aldo Garza-González, Elvira Camacho-Corona, María del Rayo |
author_facet | Clemente-Soto, Aldo F. Balderas-Rentería, Isaías Rivera, Gildardo Segura-Cabrera, Aldo Garza-González, Elvira Camacho-Corona, María del Rayo |
author_sort | Clemente-Soto, Aldo F. |
collection | PubMed |
description | The isolation and characterization of the lignan meso-dihydroguaiaretic acid (MDGA) from Larrea tridentata and its activity against Mycobacterial tuberculosis has been demonstrated, but no information regarding its mechanism of action has been documented. Therefore, in this study we carry out the gene expression from total RNA obtained from M. tuberculosis H37Rv treated with MDGA using microarray technology, which was validated by quantitative real time polymerase chain reaction. Results showed that the alpha subunit of coenzyme A transferase of M. tuberculosis H37Rv is present in both geraniol and 1-and 2-methylnaphthalene degradation pathways, which are targeted by MDGA. This assumption was supported by molecular docking which showed stable interaction between MDGA with the active site of the enzyme. We propose that inhibition of coenzyme A transferase of M. tuberculosis H37Rv results in the accumulation of geraniol and 1-and 2-methylnaphtalene inside bacteria, causing membrane destabilization and death of the pathogen. The natural product MDGA is thus an attractive template to develop new anti-tuberculosis drugs, because its target is different from those of known anti-tubercular agents. |
format | Online Article Text |
id | pubmed-6271217 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62712172018-12-28 Potential Mechanism of Action of meso-Dihydroguaiaretic Acid on Mycobacterium tuberculosis H37Rv Clemente-Soto, Aldo F. Balderas-Rentería, Isaías Rivera, Gildardo Segura-Cabrera, Aldo Garza-González, Elvira Camacho-Corona, María del Rayo Molecules Article The isolation and characterization of the lignan meso-dihydroguaiaretic acid (MDGA) from Larrea tridentata and its activity against Mycobacterial tuberculosis has been demonstrated, but no information regarding its mechanism of action has been documented. Therefore, in this study we carry out the gene expression from total RNA obtained from M. tuberculosis H37Rv treated with MDGA using microarray technology, which was validated by quantitative real time polymerase chain reaction. Results showed that the alpha subunit of coenzyme A transferase of M. tuberculosis H37Rv is present in both geraniol and 1-and 2-methylnaphthalene degradation pathways, which are targeted by MDGA. This assumption was supported by molecular docking which showed stable interaction between MDGA with the active site of the enzyme. We propose that inhibition of coenzyme A transferase of M. tuberculosis H37Rv results in the accumulation of geraniol and 1-and 2-methylnaphtalene inside bacteria, causing membrane destabilization and death of the pathogen. The natural product MDGA is thus an attractive template to develop new anti-tuberculosis drugs, because its target is different from those of known anti-tubercular agents. MDPI 2014-12-02 /pmc/articles/PMC6271217/ /pubmed/25474289 http://dx.doi.org/10.3390/molecules191220170 Text en © 2014 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 license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Clemente-Soto, Aldo F. Balderas-Rentería, Isaías Rivera, Gildardo Segura-Cabrera, Aldo Garza-González, Elvira Camacho-Corona, María del Rayo Potential Mechanism of Action of meso-Dihydroguaiaretic Acid on Mycobacterium tuberculosis H37Rv |
title | Potential Mechanism of Action of meso-Dihydroguaiaretic Acid on Mycobacterium tuberculosis H37Rv |
title_full | Potential Mechanism of Action of meso-Dihydroguaiaretic Acid on Mycobacterium tuberculosis H37Rv |
title_fullStr | Potential Mechanism of Action of meso-Dihydroguaiaretic Acid on Mycobacterium tuberculosis H37Rv |
title_full_unstemmed | Potential Mechanism of Action of meso-Dihydroguaiaretic Acid on Mycobacterium tuberculosis H37Rv |
title_short | Potential Mechanism of Action of meso-Dihydroguaiaretic Acid on Mycobacterium tuberculosis H37Rv |
title_sort | potential mechanism of action of meso-dihydroguaiaretic acid on mycobacterium tuberculosis h37rv |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271217/ https://www.ncbi.nlm.nih.gov/pubmed/25474289 http://dx.doi.org/10.3390/molecules191220170 |
work_keys_str_mv | AT clementesotoaldof potentialmechanismofactionofmesodihydroguaiareticacidonmycobacteriumtuberculosish37rv AT balderasrenteriaisaias potentialmechanismofactionofmesodihydroguaiareticacidonmycobacteriumtuberculosish37rv AT riveragildardo potentialmechanismofactionofmesodihydroguaiareticacidonmycobacteriumtuberculosish37rv AT seguracabreraaldo potentialmechanismofactionofmesodihydroguaiareticacidonmycobacteriumtuberculosish37rv AT garzagonzalezelvira potentialmechanismofactionofmesodihydroguaiareticacidonmycobacteriumtuberculosish37rv AT camachocoronamariadelrayo potentialmechanismofactionofmesodihydroguaiareticacidonmycobacteriumtuberculosish37rv |