Synthesis and biological evaluation of pyrazolopyrimidines as potential antibacterial agents.
Bioorg Med Chem Lett
; 25(24): 5699-704, 2015 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-26584881
ABSTRACT
The fragment FOL7185 (compound 17) was found to be a hit against IspD and IspE enzymes isolated from bacteria, and a series of analogs containing the pyrazolopyrimidine core were synthesized. The majority of these compounds inhibited the growth of Burkholderia thailandensis (Bt) and Pseudomonas aeruginosa (Pa) in the KirbyBauer disk diffusion susceptibility test. Compound 29 shows inhibitory activity at 0.1 mM (32.2 lg/mL), which is comparable to the control compound kanamycin (48.5 lg/mL). Compound 29 also shows inhibitory activity at 0.5 mM against kanamycin resistant P. aeruginosa. Saturation transfer difference NMR (STD-NMR) screening of these compounds against BtIspD and BtIspE indicated that most of these compounds significantly interact with BtIspE, suggesting that the compounds may inhibit the growth of Bt by disrupting isoprenoid biosynthesis. Ligand epitope mapping of compound 29 with BtIspE indicated that hydrogens on 2,4-dichlorophenyl group have higher proximity to the surface of the enzyme than hydrogens on the pyrazolopyrimidine ring.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Piridinas
/
Antibacterianos
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos