@article{5611bfd0fcef11ddb219000ea68e967b,
title = "Rational design and synthesis of new quorum-sensing inhibitors derived from acylated homoserine lactones and natural products from garlic",
abstract = "Parallel solution-phase synthesis of sulfide AHL analogues (10a-s) by one-pot or a sequential approach is reported. The corresponding sulfoxides 13a-e and sulfones 14a-e were prepared to expand the diversity of the 19-member array of sulfides . Likewise, dithianes 12a-c were prepared with similarity both to sulfides 10a-s and to bioactive structures from garlic. Design and biological screening of all compounds presented in this work targeted inhibition of quorum-sensing comprising competitive inhibition of transcriptional regulators LuxR and LasR. The design was based on critical interactions within the binding-site and structural motifs in molecular components isolated from garlic, 7 and 8, shown to be quorum-sensing inhibitors but not antibiotics. A potent quorum-sensing inhibitor N-(heptylsulfanylacetyl)-l-homoserine lactone (10c) was identified. Together with data collected for the other analogues, the resulting structure-activity relationship led to a hypothesis in which competitive binding was assumed.",
author = "Tobias Persson and Hansen, {Thomas H} and Rasmussen, {Thomas B} and Skinders{\o}, {Mette E} and Michael Givskov and John Nielsen",
note = "Keywords: 4-Butyrolactone; Biological Products; Drug Design; Garlic; Microbial Sensitivity Tests; Molecular Structure; Pseudomonas aeruginosa; Structure-Activity Relationship",
year = "2004",
doi = "10.1039/b415761c",
language = "English",
volume = "3",
pages = "253--62",
journal = "Organic & Biomolecular Chemistry",
issn = "1477-0520",
publisher = "Royal Society of Chemistry",
number = "2",
}