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Efflux pump inhibitors of clinically relevant multidrug resistant bacteria [Elektronski vir]Lamut, Andraž ...Bacterial infections are an increasingly serious issue worldwide. The inability of existing therapies to treat multidrug-resistant pathogens has been recognized as an important challenge of the 21st ... century. Efflux pumps are important in both intrinsic and acquired bacterial resistance and identification of small molecule efflux pump inhibitors (EPIs), capable of restoring the effectiveness of available antibiotics, is an active research field. In the last two decades, much effort has been made to identify novel EPIs. However, none of them has so far been approved for therapeutic use. In this article, we explore different structural families of currently known EPIs for multidrug resistance efflux systems in the most extensively studied pathogens (NorA in Staphylococcus aureus, AcrAB-TolC in Escherichia coli, and MexAB-OprM in Pseudomonas aeruginosa). Both synthetic and natural compounds are described, with structure%activity relationship studies and optimization processes presented systematically for each family individually. In vitro activities against selected test strains are presented in a unifying manner for all the EPIs described, together with the most important toxicity, pharmacokinetic and in vivo efficacy data. A critical evaluation of lead-likeness characteristics and the potential for clinical development of the most promising inhibitors of the three efflux systems is described. This overview of EPIs is a good starting point for the identification of novel effective antibacterial drugs.Source: Medicinal research reviews. - ISSN 1098-1128 (Vol. 39, iss. 6, 2019, str. 2460-2504)Type of material - e-articlePublish date - 2019Language - englishCOBISS.SI-ID - 4706929
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Database name | Field | Year |
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Lamut, Andraž | 37669 |
Peterlin-Mašič, Lucija | 19317 |
Kikelj, Danijel | 01463 |
Tomašič, Tihomir | 28334 |
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