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Antimicrobial Activity of a Library of Thioxanthones and Their Potential as Efflux Pump Inhibitors
- Source :
- Pharmaceuticals, Vol 14, Iss 572, p 572 (2021), Pharmaceuticals, Volume 14, Issue 6
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- The overexpression of efflux pumps is one of the causes of multidrug resistance, which leads to the inefficacy of drugs. This plays a pivotal role in antimicrobial resistance, and the most notable pumps are the AcrAB-TolC system (AcrB belongs to the resistance-nodulation-division family) and the NorA, from the major facilitator superfamily. In bacteria, these structures can also favor virulence and adaptation mechanisms, such as quorum-sensing and the formation of biofilm. In this study, the design and synthesis of a library of thioxanthones as potential efflux pump inhibitors are described. The thioxanthone derivatives were investigated for their antibacterial activity and inhibition of efflux pumps, biofilm formation, and quorum-sensing. The compounds were also studied for their potential to interact with P-glycoprotein (P-gp, ABCB1), an efflux pump present in mammalian cells, and for their cytotoxicity in both mouse fibroblasts and human Caco-2 cells. The results concerning the real-time ethidium bromide accumulation may suggest a potential bacterial efflux pump inhibition, which has not yet been reported for thioxanthones. Moreover, in vitro studies in human cells demonstrated a lack of cytotoxicity for concentrations up to 20 µM in Caco-2 cells, with some derivatives also showing potential for P-gp modulation.
- Subjects :
- 0301 basic medicine
03.03. Egészségtudományok
thioxanthones
efflux pumps
030106 microbiology
Pharmaceutical Science
quorum-sensing
Article
biofilm
03 medical and health sciences
Pharmacy and materia medica
Drug Discovery
antimicrobial resistance
Cytotoxicity
Chemistry
Biofilm
01.06. Biológiai tudományok
Antimicrobial
In vitro
Major facilitator superfamily
Multiple drug resistance
RS1-441
Quorum sensing
030104 developmental biology
Biochemistry
Molecular Medicine
Medicine
Efflux
Subjects
Details
- Language :
- English
- ISSN :
- 14248247
- Volume :
- 14
- Issue :
- 572
- Database :
- OpenAIRE
- Journal :
- Pharmaceuticals
- Accession number :
- edsair.doi.dedup.....6df9049bf59da6161cb281edb1e46c32