Synthesis and evaluation of new antagonists of bacterial quorum sensing in Vibrio harveyi.
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.
Peng
Hanjing
H
Department of Chemistry and Center for Biotechnology and Drug Design, Georgia State University, P.O. Box 4098, Atlanta, GA 30302-4098, USA.
Cheng
Yunfeng
Y
Ni
Nanting
N
Li
Minyong
M
Choudhary
Gaurav
G
Chou
Han Ting
HT
Lu
Chung-Dar
CD
Tai
Phang C
PC
Wang
Binghe
B
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
C545853:KM 03009; D007783:Lactones; C091088:N-octanoylhomoserine lactone; C545854:SPB 02229; D013450:Sulfones; D013854:Thioamides; D006714:Homoserine