Synthesis, antimycobacterial evaluation, and QSAR analysis of meso-dihydroguaiaretic acid derivatives
Por:
Chavez-Villarreal, Karen G., Garcia, Abraham, Romo-Mancillas, Antonio, Garza-Gonzalez, Elvira, Waksman de Torres, Noemi, Miranda, Luis D., Moo-Puc, Rosa Esther, Chale-Dzul, Juan, del Rayo Camacho-Corona, Maria
Publicada:
1 abr 2018
Resumen:
The increasing incidence of new tuberculosis cases and multidrug-resistant (MDR) strains of Mycobacterium tuberculosis have drawn the attention of researchers to the chemical derivatization of promising antimycobacterial natural products. Meso-dihydroguaiaretic acid (meso-DGA) has reported to possess modest activity against sensitive (H37Rv) and resistant M. tuberculosis strains. To improve the antimycobacterial properties of meso-DGA, a series of 19 meso-DGA derivatives bearing carbamates and ethers were synthesized and tested against H37Rv and two MDR strains. Among the carbamates, 2, 3, 5, and 6 exhibited the lowest minimal inhibitory concentration (MIC) values against one MDR strain (MICs of 25 and 12.5 µg/mL), with 6 being the most lipophilic and potent. On the other hand, ethers 10, 12, 14, and 18 showed MIC values in the range of 6.25–50 µg/mL against the three strains, with 14 being the most potent. The larger the chain length in the mono-alkenylated ethers (10, 12, and 14), the lower the MIC value; moreover, a correlation between the chain length of these ethers and the lipophilic character and antimycobacterial activity was observed. The safety profile of the most bioactive derivatives 6 and 14 indicated that 6 (SI > 10) was more toxic to sensitive and MDR strains than to Vero cells, whereas 14 (SI < 3) was more toxic to mammalian cells than to M. tuberculosis strains. Nevertheless, the safety profile of 6 and the potent antimycobacterial activity of 14 make them potential candidates for further studies. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.
Filiaciones:
Chavez-Villarreal, Karen G.:
Univ Autonoma Nuevo Leon, Fac Ciencias Quim, Ave Univ S-N,Ciudad Univ, San Nicolas De Los Garza 66455, Nuevo Leon, Mexico
Garcia, Abraham:
Univ Autonoma Nuevo Leon, Fac Ciencias Quim, Ave Univ S-N,Ciudad Univ, San Nicolas De Los Garza 66455, Nuevo Leon, Mexico
Romo-Mancillas, Antonio:
Univ Autonoma Queretaro, Fac Quim, Ctr Univ, Queretaro 76010, Queretaro, Mexico
Garza-Gonzalez, Elvira:
Univ Autonoma Nuevo Leon, Serv Gastroenterol, Monterrey 64460, Nuevo Leon, Mexico
Hosp Univ Dr Jose Eleuterio Gonzalez Madero & Agu, Dept Patol Clin, Mitras Ctr, Monterrey 64460, Nuevo Leon, Mexico
Waksman de Torres, Noemi:
Univ Autonoma Nuevo Leon, Fac Med Madero & Aguirre Pequeno, Mitras Ctr, Monterrey 64460, Nuevo Leon, Mexico
Miranda, Luis D.:
Univ Nacl Autonoma Mexico, Inst Quim, Circuito Exterior S-N,Ciudad Univ, Mexico City 04510, DF, Mexico
Moo-Puc, Rosa Esther:
IMSS, Unidad Invest Med Yucatan, Unidad Med Alta Especialidad, Ctr Med Ignacio Garcia Tellez, Calle 41 439, Merida, Yucatan, Mexico
Chale-Dzul, Juan:
IMSS, Lab Vigilancia & Invest Epidemiol, Unidad Med Alta Especialidad, Ctr Med Ignacio Garcia Tellez, Merida 97150, Yucatan, Mexico
del Rayo Camacho-Corona, Maria:
Univ Autonoma Nuevo Leon, Fac Ciencias Quim, Ave Univ S-N,Ciudad Univ, San Nicolas De Los Garza 66455, Nuevo Leon, Mexico
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