2. Academic Validation
  3. meso-Dihydroguaiaretic acid derivatives with antibacterial and antimycobacterial activity

meso-Dihydroguaiaretic acid derivatives with antibacterial and antimycobacterial activity

  • Bioorg Med Chem. 2017 Oct 15;25(20):5247-5259. doi: 10.1016/j.bmc.2017.07.047.
Karen Reyes-Melo 1,  Abraham García 2,  Antonio Romo-Mancillas 3,  Elvira Garza-González 4,  Verónica M Rivas-Galindo 5,  Luis D Miranda 6,  Javier Vargas-Villarreal 7,  Juan Manuel J Favela-Hernández 1,  María Del Rayo Camacho-Corona 8
Affiliations

Affiliations

  • 1 Universidad Autónoma de Nuevo León, Facultad de Ciencias Químicas, Av. Universidad s/n, Ciudad Universitaria, C.P. 66455 San Nicolás de los Garza, Nuevo León, Mexico.
  • 2 Universidad Autónoma de Nuevo León, Facultad de Ciencias Químicas, Av. Universidad s/n, Ciudad Universitaria, C.P. 66455 San Nicolás de los Garza, Nuevo León, Mexico. Electronic address: edgar.garciazp@uanl.edu.mx.
  • 3 Facultad de Química, Universidad Autónoma de Querétaro, Centro Universitario, Cerro de las Campanas, C.P. 76010 Querétaro, Querétaro, Mexico.
  • 4 Universidad Autónoma de Nuevo León, Servicio de Gastroenterología y Departamento de Patología Clínica, Hospital Universitario Dr. José Eleuterio González, Madero y Aguirre Pequeño, Mitras Centro, C.P. 64460 Monterrey, Nuevo León, Mexico.
  • 5 Universidad Autónoma de Nuevo León, Facultad de Medicina, Madero y Aguirre Pequeño, Mitras Centro, C.P. 64460 Monterrey, Nuevo León, Mexico.
  • 6 Universidad Nacional Autónoma de México, Instituto de Química, Circuito Exterior s/n, Ciudad universitaria, Coyoacán C.P. 04510, Ciudad de México, Mexico.
  • 7 Instituto Mexicano del Seguro Social, Centro de Investigación Biomédica del Noreste, División de Biología Celular y Molecular, Laboratorio de Bioquímica y Fisiología Celular, Administración de correos No. 4, Apartado Postal 020-E, Col. Independencia, C.P. 64720 Monterrey, Nuevo León, Mexico.
  • 8 Universidad Autónoma de Nuevo León, Facultad de Ciencias Químicas, Av. Universidad s/n, Ciudad Universitaria, C.P. 66455 San Nicolás de los Garza, Nuevo León, Mexico. Electronic address: maria.camachocn@uanl.edu.mx.
PMID: 28844400 DOI: 10.1016/j.bmc.2017.07.047
Abstract

Thirty-three meso-dihydroguaiaretic acid (meso-DGA) derivatives bearing esters, ethers, and amino-ethers were synthesized. All derivatives were tested against twelve drug-resistant clinical isolates of Gram-positive and Gram-negative bacteria, including sensitive (H37Rv) and multidrug-resistant Mycobacterium tuberculosis strains. Among the tested compounds, four esters (7, 11, 13, and 17), one ether (23), and three amino-ethers (30, 31, and 33) exhibited moderate activity against methicillin-resistant Staphylococcus aureus, whereas 30 and 31 showed better results than levofloxacin against vancomycin-resistant Enterococcus faecium. Additionally, nineteen meso-DGA derivatives displayed moderate to potent activity against M. tuberculosis H37Rv with minimum inhibitory concentration (MIC) values ranging from 3.125 to 50µg/mL. Seven meso-DGA derivatives bearing amino-ethers (26-31 and 33) exhibited the lowest MICs against M. tuberculosis H37Rv and G122 strains, with 31 being as potent as ethambutol (MICs of 3.125 and 6.25µg/mL). The presence of positively charged group precursors possessing steric and hydrophobic features (e.g. N-ethylpiperidine moieties in meso-31) resulted essential to significantly increase the antimycobacterial properties of parent meso-DGA as supported by the R-group pharmacophoric and field-based QSAR analyses. To investigate the safety profile of the antimycobacterial compounds, cytotoxicity on Vero cells was determined. The amino-ether 31 exhibited a selectivity index value of 23, which indicate it was more toxic to M. tuberculosis than to mammalian cells. Therefore, 31 can be considered as a promising antitubercular agent for further studies.

Keywords

Antibacterial; Antimycobacterial; Lignans; Selectivity index; meso-Dihydroguaiaretic acid.

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