Modified ToxT inhibitor reduces Vibrio cholerae virulence in vivo
| Autor: | Gabriela Kovacikova, Anne K Woodbrey, Gordon W. Gribble, F. Jon Kull, Evans O. Onyango |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
030106 microbiology Virulence medicine.disease_cause Biochemistry Article Microbiology 03 medical and health sciences Mice Bacterial Proteins Cholera In vivo medicine Animals Intestinal Mucosa Transcription factor Vibrio cholerae Regulation of gene expression Bicyclic molecule Chemistry Biological activity Gene Expression Regulation Bacterial In vitro Anti-Bacterial Agents 030104 developmental biology Animals Newborn Transcription Factors |
| Popis: | We have previously designed and synthesized small-molecule inhibitors that reduce Vibrio cholerae virulence in vitro by targeting the transcription factor ToxT. Here we report the synthesis and biological activity of derivatives of our previous bicyclic, fatty acid-like inhibitors. All of the synthesized derivatives show antivirulence activity in vitro. For the most potent compounds, a concentration of 5 μM completely inhibited ToxT-mediated tcpA expression as measured in the β-galactosidase assay. One indole compound, 3-(1-butyl-1 H-indol-7-yl)propanoic acid (8), was also effective at inhibiting intestinal colonization in the infant mouse. These modified compounds may serve as good candidates for further anti-cholera drug development. |
| Databáze: | OpenAIRE |
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