التفاصيل البيبلوغرافية
| العنوان: |
Auranofin and N-heterocyclic carbene gold-analogs are potent inhibitors of the bacteria Helicobacter pylori. |
| المؤلفون: |
Owings, Joshua P.1, McNair, Nina N.1,2, Yiu Fung Mui3,4, Gustafsson, Tomas N.5, Holmgren, Arne5, Contel, Maria3,4, Goldberg, Joanna B.1, Mead, Jan R.1,2 jmead@emory.edu |
| المصدر: |
FEMS Microbiology Letters. Jul2016, Vol. 363 Issue 14, p1-6. 6p. 1 Diagram, 2 Charts, 2 Graphs. |
| مصطلحات موضوعية: |
*AURANOFIN, *ANTIARTHRITIC agents, *RHEUMATOID arthritis treatment, *HETEROCYCLIC compounds, *THIOREDOXIN reductase (NADPH), *HELICOBACTER pylori, *THERAPEUTICS |
| مستخلص: |
Auranofin is an FDA-approved gold-containing compound used for the treatment of rheumatoid arthritis. Recent reports of antimicrobial activity against protozoa and bacteria indicates auranofin targets the reductive enzyme thioredoxin reductase (TrxR). We evaluated auranofin as well as 5 auranofin analogs containing N-heterocyclic carbenes (instead of the triethylphosphane present in auranofin) and 5 gold-carbene controls for their ability to inhibit or kill Helicobacter pylori in vitro. Auranofin completely inhibited bacterial growth at 1.2 µM. Purified H. pylori TrxR was inhibited by auranofin in a cell-free assay (IC50 ~88 nM). The most active gold(I)-N-heterocyclic carbene compounds exhibited MICs comparable to auranofin against H. pylori (2 µM) while also exhibiting lower toxicities for human embryonic kidney cells (HEK-293T cells). Median toxic concentrations (TC50) were 13-20 fold higher compared to auranofin indicating they were less cytotoxic. The N-heterocyclic carbene analogs maybe well tolerated, but further evaluation is needed in vivo. Finally, auranofin was synergistic with the antibiotic amoxicillin suggesting that targeting both the reductive enzyme TrxR and cell wall synthesis may be effective against H. pylori infections. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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