RT Journal Article
T1 Aromatic esters of bicyclic amines as antimicrobials against Streptococcus pneumoniae
A1 Retamosa, María
A1 Díez-Martínez, Roberto
A1 Maestro García-Donas, María Beatriz
A1 García-Fernández, Esther
A1 de Waal, Bas
A1 Meijer, Bert
A1 García, Pedro
A1 Sanz, Jesús
AB 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 in 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.
PB Wiley 
SN 0044-8249
YR 2015
FD 2015
LK https://hdl.handle.net/20.500.14352/95491
UL https://hdl.handle.net/20.500.14352/95491
LA eng
NO De Gracia Retamosa, María, et al. «Aromatic Esters of Bicyclic Amines as Antimicrobials against Streptococcus Pneumoniae». Angewandte Chemie International Edition, vol. 54, n.o 46, noviembre de 2015, pp. 13673-77.  https://doi.org/10.1002/anie.201505700.
NO AcknowledgementsThis work was supported by grants BFU2010-17824 and BIO2013-47684-R (Spanish Ministry of Education and Science), and EU-CP223111 (CAREPNEUMO, European Union). We thank M. Gutiérrez and J. Casanova for excellent technical assistance.
NO Ministerio de Educación (España)
NO European Commission
DS Docta Complutense
RD 13 abr 2025