FabI (enoyl acyl carrier protein reductase) - A potential broad spectrum therapeutic target and its inhibitors.
Eur J Med Chem
; 208: 112757, 2020 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-32883635
ABSTRACT
Development of new anti-bacterial agents acting upon underexploited targets and thus evading known mechanisms of resistance is the need of the hour. The highly conserved and distinct bacterial fatty acid biosynthesis pathway (FAS-II), presents a validated and yet relatively underexploited target for drug discovery. FabI and its isoforms (FabL, FabK, FabV and InhA) are essential enoyl-ACP reductases present in several microorganisms. In addition, the components of the FAS-II pathway are distinct from the multi-enzyme FAS-I complex found in mammals. Thus, inhibition of FabI and its isoforms is anticipated to result in broad-spectrum antibacterial activity. Several research groups from industry and academic laboratories have devoted significant efforts to develop effective FabI-targeting antibiotics, which are currently in various stages of clinical development for the treatment of multi-drug resistant bacterial infections. This review summarizes all the natural as well as synthetic inhibitors of gram-positive and gram-negative enoyl ACP reductases (FabI). The knowledge of the reported inhibitors can aid in the development of broad-spectrum antibacterials specifically targeting FabI enzymes from S. aureus, S. epidermidis, B. anthracis, B. cereus, E. coli, P. aeruginosa, P. falciparum and M. tuberculosis.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Compostos Orgânicos
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Inibidores Enzimáticos
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Enoil-(Proteína de Transporte de Acila) Redutase (NADH)
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Antibacterianos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article