| Autor: |
Macielag, M. J., Demers, J. P., Fraga-Spano, S. A., Hlasta, D. J., Johnson, S. G., Kanojia, R. M., Russell, R. K., Sui, Z., Weidner-Wells, M. A., Werblood, H., Foleno, B. D., Goldschmidt, R. M., Loeloff, M. J., Webb, G. C., Barrett, J. F. |
| Zdroj: |
Journal of Medicinal Chemistry; July 30, 1998, Vol. 41 Issue: 16 p2939-2945, 7p |
| Abstrakt: |
A new class of inhibitors of the two-component regulatory systems (TCS) of bacteria was discovered based on the salicylanilide screening hits, closantel (1) and tetrachlorosalicylanilide (9). A systematic SAR study versus a model TCS, KinA/Spo0F, demonstrated the importance of electron-attracting substituents in the salicyloyl ring and hydrophobic groups in the anilide moiety for optimal activity. In addition, derivatives 8 and 16, containing the 2,3-dihydroxybenzanilide structural motif, were potent inhibitors of the autophosphorylation of the KinA kinase, with IC50s of 2.8 and 6.3 μM, respectively. Compound 8 also inhibited the TCS mediating vancomycin resistance (VanS/VanR) in a genetically engineered Enterococcus faecalis cell line at concentrations subinhibitory for growth. Closantel (1), tetrachlorosalicylanilide (9), and several related derivatives (2, 7, 10, 11, 20) had antibacterial activity against the drug-resistant organisms, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF). |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
