Drug Repositioning as a Therapeutic Strategy against Streptococcus pneumoniae: Cell Membrane as Potential Target
Investigation article published in International Journal of Molecualr Sciences
March 18th, 2023
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
Ortiz-Miravalles L., Sanchez-Angulo M., Sanz JM. and Maestro B.
 | Protein Engineering against Antimicrobial Resistance Group. Centro de Investigaciones Biológicas Margarita Salas. Consejo Superior de Investigaciones Científicas (CSIC). |
 | Departamento de Sanidad Animal. Facultad de Veterinaria. Universidad Complutense (UCM). |
| Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM). |
 | Universidad Miguel Hernández (UMH). |
 | Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES). Instituto de Salud Carlos III (ISCIII). |
| Departamento de Bioquímica y Biología Molecular. Facultad de Ciencias Biológicas. Universidad Complutense (UCM). |
