title: Synthesis and evaluation of new antagonists of bacterial quorum sensing in Vibrio harveyi.
abstract: Bacterial quorum sensing has received much attention in recent years because of its relevance to pathological events such as biofilm formation. Based on the structures of two lead inhibitors (IC50: 35-55 microM) against autoinducer-2-mediated quorum sensing identified through virtual screening, we synthesized 39 analogues and examined their inhibitory activities. Twelve of these new analogues showed equal or better inhibitory activities than the lead inhibitors. The best compound showed an IC50 value of approximately 6 microM in a whole-cell assay using Vibrio harveyi as the model organism. The structure-activity relationship is discussed herein.
authors.affiliation: Department of Chemistry and Center for Biotechnology and Drug Design, Georgia State University, P.O. Box 4098, Atlanta, GA 30302-4098, USA.
authors.forename: Hanjing
authors.initials: H
authors.lastname: Peng
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Cheng
authors.forename: Nanting
authors.initials: N
authors.lastname: Ni
authors.forename: Minyong
authors.initials: M
authors.lastname: Li
authors.forename: Gaurav
authors.initials: G
authors.lastname: Choudhary
authors.forename: Han Ting
authors.initials: HT
authors.lastname: Chou
authors.forename: Chung-Dar
authors.initials: CD
authors.lastname: Lu
authors.forename: Phang C
authors.initials: PC
authors.lastname: Tai
authors.forename: Binghe
authors.initials: B
authors.lastname: Wang
mesh_terms: D015195:Drug Design; D006714:Homoserine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology; D053038:Quorum Sensing / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013854:Thioamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014733:Vibrio / Q000187:drug effects* / Q000378:metabolism
chemical_list: C545853:KM 03009; D007783:Lactones; C091088:N-octanoylhomoserine lactone; C545854:SPB 02229; D013450:Sulfones; D013854:Thioamides; D006714:Homoserine