Drug Repositioning as a Therapeutic Strategy against <i>Streptococcus pneumoniae</i>: Cell Membrane as Potential Target
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 <i>Streptococcus pneumoniae</i>. After four discrimination rounds, a set of seven...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/6/5831 |
| Summary: | 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 <i>Streptococcus pneumoniae</i>. 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. |
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| ISSN: | 1661-6596 1422-0067 |