Discovery of potent inhibitors of pseudomonal quorum sensing via pharmacophore modeling and in silico screening

HipHop-Refine was employed to derive a binding hypothesis for pseudomonal quorum sensing (QS) antagonists. The model was employed as 3D search query to screen the National Cancer Institute (NCI) database. One of the hits illustrated nanomolar QS inhibitory activity. The fact that this compound contained tetravalent lead (Pb) prompted us to evaluate the activities of phenyl mercuric nitrate and thimerosal, both fit the binding pharmacophore. The two mercurials illustrated nanomolar to low micromolar IC50 inhibitory values against pseudomonal QS. The three compounds represent a new class of QS inhibitors.

Graphical abstractIn silico-based discovery of new potent pseudomonal quorum sensing inhibitors is reported.Figure optionsDownload full-size imageDownload as PowerPoint slide