Discovery of bicyclic inhibitors against menaquinone biosynthesis.
Future Med Chem
; 8(1): 11-6, 2016 Jan.
Article
em En
| MEDLINE
| ID: mdl-26699277
ABSTRACT
INTRODUCTION:
Menaquinone is used for transporting electrons and is essential for the aerobic and anaerobic respiratory systems of all pathogens and prokaryotes. Many Gram-positive bacteria use only menaquinone in the electron transport system. Thus, menaquinone biosynthesis is a potential target for the development of inhibitors against bacteria including drug-resistant pathogens.RESULTS:
After modeling, synthesis and in vitro testing, we determined that 7-methoxy-2-naphthol-based inhibitors targeted the MenA enzyme of the menaquinone biosynthesis pathway. The developmental compounds 1 and 2 were active against Mycobacterium tuberculosis and methicillin-resistant Staphylococcus aureus with a minimal inhibitory concentration of 3-5 µg/ml.CONCLUSION:
Nontraditional bicyclic inhibitors, compounds 1 and 2 could serve as lead compounds for the development of an antimicrobial agent, with activities against M. tuberculosis and methicillin-resistant S. aureus.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
/
Compostos Bicíclicos com Pontes
/
Alquil e Aril Transferases
/
Vitamina K 2
/
Inibidores Enzimáticos
/
Descoberta de Drogas
/
Antibacterianos
/
Naftalenos
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article