Cellular Studies of an Aminoglycoside Potentiator Reveal a New Inhibitor of Aminoglycoside Resistance
| Autor: | Johans Fakhoury, Kathleen Wee, Kenward Vong, Karine Auclair, Jinming Guan, Edie Dullaghan |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.drug_class Coenzyme A Antibiotics Enterococcus faecium Pharmacology Biochemistry 03 medical and health sciences chemistry.chemical_compound Acetyltransferases Drug Resistance Bacterial medicine Escherichia coli Humans Prodrugs Molecular Biology chemistry.chemical_classification biology Organic Chemistry Aminoglycoside Potentiator Prodrug biology.organism_classification 3. Good health Anti-Bacterial Agents 030104 developmental biology Enzyme Aminoglycosides chemistry Mechanism of action Molecular Medicine medicine.symptom Bacteria HeLa Cells |
| Zdroj: | Chembiochem : a European journal of chemical biology. 19(19) |
| ISSN: | 1439-7633 |
| Popis: | Aminoglycosides are a group of broad-spectrum antibiotics that have been used in the clinic for almost a century. The rapid spread of bacterial genes coding for aminoglycoside-modifying enzymes has, however, dramatically decreased the utility of aminoglycosides. We have previously reported several aminoglycoside potentiators that work by inhibiting aminoglycoside N-6'-acetyltransferase, one of the most common determinants of aminoglycoside resistance. Among these, prodrugs that combine the structure of an aminoglycoside with that of pantothenate into one molecule are especially promising. We report here a series of cellular studies to investigate the activity and mechanism of action of these prodrugs further. Our results reveal a new aminoglycoside resistance inhibitor, as well as the possibility that these prodrugs are transformed into more than one inhibitor in bacteria. We also report that the onset of the potentiators is rapid. Their low cell cytotoxicity, good stability, and potentiation of various aminoglycosides, against both Gram-positive and Gram-negative bacteria, make them interesting compounds for the development of new drugs. |
| Databáze: | OpenAIRE |
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