Aromatic Esters of Bicyclic Amines as Antimicrobials against Streptococcus pneumoniae.
Angew Chem Int Ed Engl
; 54(46): 13673-7, 2015 Nov 09.
Article
em En
| MEDLINE
| ID: mdl-26377931
ABSTRACT
A double approach was followed in the search of novel inhibitors of the surface choline-binding proteins (CBPs) of Streptococcus pneumoniae (pneumococcus) with antimicrobial properties. First, a library of 49 rationally-designed esters of alkyl amines was screened for their specific binding to CBPs. The best binders, being esters of bicyclic amines (EBAs), were then tested for their inâ
vitro effect on pneumococcal growth and morphology. Second, the efficiency of EBA-induced CBP inhibition was enhanced about 45,000-fold by multivalency effects upon synthesizing a poly(propylene imine) dendrimer containing eight copies of an atropine derivative. Both approaches led to compounds that arrest bacterial growth, dramatically decrease cell viability, and exhibit a protection effect in animal disease models, demonstrating that the pneumococcal CBPs are adequate targets for the discovery of novel antimicrobials that overcome the currently increasing antimicrobial resistance issues.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Infecções Pneumocócicas
/
Streptococcus pneumoniae
/
Ésteres
/
Aminas
/
Antibacterianos
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article