SMALL MOLECULE ANTAGONISTS OF BACTERIAL QUORUM-SENSING RECEPTORS

摘要

A novel small molecule antagonizes two types of acyl homoserine lactone receptors: membrane-bound and cytoplasmic. A focused library of analogs and derivatives of the original antagonist was synthesized. Analog and derivative molecules harbor a range of activities. The novel small molecule and most potent antagonist protects the eukaryote Caenorhabditis elegans from quorum-sensing-mediated killing by the bacterial pathogen Chromobacterium violaceum. The saving of C. elegans demonstrates the use of these molecules as small molecule antimicrobials.

主权项

1. A small molecule analog of 4-(4-chloro-2-methylphenoxy)-N-(2-oxotetrahydrothiophen-3-yl)butanamide wherein said small molecule is represented by the formula: wherein X is O or S; n is 0, 1 or 2; Y is O, S or CH2; and Z is a halogen, hydroxyl, alkoxyl, cyano, nitro, amido, acetamido, amino, alkylamino, aryl, heteroaryl, acyl, alkyl, cycloalkyl, sulfonamide, alkyl sulfonamide or a combination thereof; and wherein Z is located at the ortho, meta or para position or at a combination thereof.