Format

Send to

Choose Destination
Org Biomol Chem. 2005 Jan 21;3(2):253-62. Epub 2004 Dec 1.

Rational design and synthesis of new quorum-sensing inhibitors derived from acylated homoserine lactones and natural products from garlic.

Author information

1
Department of Natural Sciences, Bioorganic Chemistry Section, Royal Veterinary and Agricultural University, Frederiksberg C, DK-1871, Denmark.

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.

PMID:
15632967
DOI:
10.1039/b415761c
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Royal Society of Chemistry
Loading ...
Support Center