Synthesis of thiophenones as quorum sensing inhibitors

Abstract

Bacteria communicate using small signaling molecules as part of a system of communication called quorum sensing (QS) to control gene expression for synchronized bacterial behaviors. A task performed by bacteria that is often controlled by this means is biofilm production, making bacteria more resistant to external factors. Naturally occurring furanones that were isolated from a red macroalgae have been shown to have the ability to interrupt this communication. As a result thiophenones have been synthesized and investigated as a novel class of quorum sensing inhibitors (QSIs). Molecules of this class have greater biofilm reduction abilities than furanone equivalents for some bacteria. This discovery resulted in many more thiophenones with a variety of functional groups being synthesized using both classical and new methods. These compounds have been used in biological assays to determine their quorum sensing inhibition (QSI) potential, and have shown promising results. In this study tiobovolide has been synthesized and confirmed to exhibit some QSI properties. In addition to this trifluoromethyllated thiophenones have been synthesized and tested for QSI ability. It was found that most exhibited QSI properties, but that compounds with methyl groups in the 3- and 4-position showed no biological activity. This finding may support a 1,6-Michael-type reaction mechanism that has been suggested to be responsible for bioactivity.