RT Journal Article
T1 Drug Repositioning as a Therapeutic Strategy against Streptococcus pneumoniae: Cell Membrane as Potential Target
A1 Ortiz Miravalles, Laura
A1 Sánchez-Angulo, Manuel
A1 Sanz, Jesús M.
A1 Maestro García-Donas, María Beatriz
AB A collection of repurposing drugs (Prestwick Chemical Library) containing 1200 compounds was screened to investigate the drugs’ antimicrobial effects against planktonic cultures of the respiratory pathogen Streptococcus pneumoniae. After four discrimination rounds, a set of seven compounds was finally selected, namely (i) clofilium tosylate; (ii) vanoxerine; (iii) mitoxantrone dihydrochloride; (iv) amiodarone hydrochloride; (v) tamoxifen citrate; (vi) terfenadine; and (vii) clomiphene citrate (Z, E). These molecules arrested pneumococcal growth in a liquid medium and induced a decrease in bacterial viability between 90.0% and 99.9% at 25 µM concentration, with minimal inhibitory concentrations (MICs) also in the micromolar range. Moreover, all compounds but mitoxantrone caused a remarkable increase in the permeability of the bacterial membrane and share a common, minimal chemical structure consisting of an aliphatic amine linked to a phenyl moiety via a short carbon/oxygen linker. These results open new possibilities to tackle pneumococcal disease through drug repositioning and provide clues for the design of novel membrane-targeted antimicrobials with a related chemical structure.
PB MPDI
SN 1422-0067
YR 2023
FD 2023-03-18
LK https://hdl.handle.net/20.500.14352/72396
UL https://hdl.handle.net/20.500.14352/72396
LA eng
NO MCIN/AEI/ 10.13039/501100011033
DS Docta Complutense
RD 5 abr 2025