RESUMEN
A series of (3-benzyl-5-hydroxyphenyl)carbamates were evaluated as new antibacterial agents. Several compounds showed potent inhibitory activity against sensitive and drug-resistant Gram-positive bacteria. The compounds are ineffective against all tested Gram-negative bacteria. The structure of the ester group exerted a profound effect on antibacterial activity. 4,4-Dimethylcyclohexanyl carbamate 6h exhibited the most potent inhibitory activity against the standard and clinically isolated Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis (minimum inhibitory concentration = 4-8 µg/ml) strains. The preliminary experimental evidence indicated that these carbamates target the bacterial cell wall and share a similar mechanism of action with vancomycin.
Asunto(s)
Antibacterianos/farmacología , Carbamatos/farmacología , Enterococcus faecalis/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Staphylococcus epidermidis/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Carbamatos/síntesis química , Carbamatos/química , Ensayos de Selección de Medicamentos Antitumorales , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Relación Estructura-ActividadRESUMEN
A series of 3-amino-5-benzylphenol derivatives were designed and synthesized. Among them, (3-benzyl-5-hydroxyphenyl)carbamates were found to exert good inhibitory activity against M. tuberculosis H37Ra, H37Rv and clinically isolated multidrug-resistant M. tuberculosis strains (MIC = 0.625-6.25 µg/mL). The privileged compounds 3i and 3l showed moderate cytotoxicity against cell line A549. Compound 3l also exhibited potent in vivo inhibitory activity on a mouse infection model via the oral administration. The results demonstrated 3-hydroxyphenylcarbamates as a class of new antitubercular agents with good potential.