Search

We have previously designed and synthesized small-molecule inhibitors that reduce Vibrio choleraevirulence in vitroby 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 tcpAexpression as measured in the β-galactosidase assay. One indole compound, 3-(1-butyl-1H-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.