Conjugation of a 5-nitrofuran-2-oyl moiety to aminoalkylimidazoles produces non-toxic nitrofurans that are efficacious in vitro and in vivo against multidrug-resistant Mycobacterium tuberculosis.
Eur J Med Chem
; 157: 1115-1126, 2018 Sep 05.
Article
en En
| MEDLINE
| ID: mdl-30179748
ABSTRACT
Within the general nitrofuran carboxamide chemotype, chimera derivatives incorporating diversely substituted imidazoles attached via an alkylamino linker were synthesized. Antimycobacterial evaluation against drug-sensitive M. tuberculosis H37Rv strain identified five active druglike compounds which were further profiled against patient-derived M. tuberculosis strains in vitro. One of the compounds displayed promising potent activity (MIC 0.8⯵g/mL) against one of such strains otherwise resistant to such first- and second-line TB therapies as streptomycin, isoniazid, rifampicin, ethambutol, kanamycin, ethionamide, capreomycin and amikacin. The compound was shown to possess low toxicity for mice (LD50â¯=â¯900.0⯱â¯83.96â¯mg/kg) and to be similarly efficacious to etambutol, in the mouse model of drug-sensitive tuberculosis, and to neurotoxic cycloserine in mice infected with MDR tuberculosis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tuberculosis Resistente a Múltiples Medicamentos
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Farmacorresistencia Bacteriana Múltiple
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Imidazoles
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Mycobacterium tuberculosis
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Nitrofuranos
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Antituberculosos
Idioma:
En
Revista:
Eur J Med Chem
Año:
2018
Tipo del documento:
Article