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.
Taha
Mutasem O
MO
Faculty of Pharmacy, University of Jordan, Amman, Jordan. mutasem@ju.edu.jo
Al-Bakri
Amal G
AG
Zalloum
Waleed A
WA
D000465:Algorithms; D001665:Binding Sites; D002412:Cations; D019295:Computational Biology; D003198:Computer Simulation; D016208:Databases, Factual; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007854:Lead / Q000737:chemistry; D009566:Nitrates / Q000737:chemistry; D010663:Phenylmercury Compounds / Q000737:chemistry; D011549:Pseudomonas / Q000187:drug effects* / Q000502:physiology; D021281:Quantitative Structure-Activity Relationship; D053038:Quorum Sensing / Q000187:drug effects* / Q000502:physiology; D013849:Thimerosal / Q000737:chemistry
D002412:Cations; D004791:Enzyme Inhibitors; D009566:Nitrates; D010663:Phenylmercury Compounds; D013849:Thimerosal; D007854:Lead