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Title: The search for new inhibitors of bacterial efflux pumps among amine derivatives of 5-arylidenehydantion
Abstract:
The purpose of this research was to find new EPIs of the AcrAB-TolC efflux system in groups amine derivatives of 5-arylidenehydantoin and 5-arylideneimidazolone. In the first stage of the research 32 new derivatives of 5-arylidenehydantoin were obtained as a result of modifications of the lead structure P2. Structures of new derivatives were confirmed by using chromatographic and spectral methods (1H-NMR, 13CNMR, IR, LC-MS, elemental analysis). Theoretical screening of the toxicity risk as well as the prediction of drug-like properties of tested derivatives were performed by using the OSIRIS program. The activity of compounds was evaluated in microbiological studies. Three strains of Enterobacter aerogenes with different expressions of the AcrAB efflux pump. The first study carried out was a susceptibility test determining the MICs of compounds. Then the effect of the compounds on bacterial susceptibility to antibiotics such as nalidixic acid, chloramphenicol, doxycycline and erythromycin was examined. After the most active compounds were detected, their type of cooperation with antibiotics was determined based on isobolograms and the FIC index calculated. The last of microbiological studies performed was the real-time efflux (RTE) assay which used the fluorescent dye 1,2’-dinaphthylamine and allowed the functioning of the pump to be monitored directly. The structure-activity ; relationship (SAR) analysis which was the last stage of the research allowed the identification of structural fragments which could be essential for blocking the AcrAB.
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Kieć-Kononowicz, Katarzyna ; Pages, Jean-Marie ; Handzlik, Jadwiga ; Alibert, Sandrine
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Last modified:
Mar 16, 2023
In our library since:
Jun 3, 2022
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http://dl.cm-uj.krakow.pl:8080/publication/4726
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| Edition name | Date |
|---|---|
| ZB-123149 | Mar 16, 2023 |
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