Design, synthesis and evaluation of novel molecules with a diphenyl ether nucleus as potential antitubercular agents.
Bioorg Med Chem Lett
; 22(2): 954-7, 2012 Jan 15.
Article
en En
| MEDLINE
| ID: mdl-22197389
ABSTRACT
A series of compounds with a diphenyl ether nucleus were synthesized by incorporating various amines into the diphenyl ether scaffold with an amide bond. Their antitubercular activities were evaluated against Mycobacterium tuberculosis H(37)Rv by a microdilution method, with MIC values ranging from 4 to 64µg/mL. Through structure-activity relationship studies, the two chlorine atoms at 3 and 4 positions in the phenyl ring of R(2) group were found to play a significant role in the antitubercular activity. The most potent compound 6c showed an MIC value of 4µg/mL and a good safety profile in HepG2 cell line by the MTT assay. Compound 6c was further found to be effective in a murine model of BCG infection, providing a good lead for subsequent optimization.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Éteres Fenílicos
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Infecciones por Mycobacterium
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Mycobacterium tuberculosis
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Antituberculosos
Tipo de estudio:
Evaluation_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2012
Tipo del documento:
Article