TY - JOUR
T1 - Potential mechanism of action of meso-dihydroguaiaretic acid on Mycobacterium tuberculosis H37Rv
AU - Clemente-Soto, Aldo F.
AU - Balderas-Rentería, Isaías
AU - Rivera, Gildardo
AU - Segura-Cabrera, Aldo
AU - Garza-González, Elvira
AU - Del Rayo Camacho-Corona, María
N1 - Publisher Copyright:
© 2014 by the authors; licensee MDPI, Basel, Switzerland.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - 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.
AB - 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.
KW - Meso-dihydroguaiaretic acid
KW - Mode of action
KW - Mycobacterium tuberculosis H37Rv
KW - Natural product
UR - http://www.scopus.com/inward/record.url?scp=84919725391&partnerID=8YFLogxK
U2 - 10.3390/molecules191220170
DO - 10.3390/molecules191220170
M3 - Artículo
C2 - 25474289
AN - SCOPUS:84919725391
SN - 1420-3049
VL - 19
SP - 20170
EP - 20182
JO - Molecules
JF - Molecules
IS - 12
ER -
