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Quorum sensing (QS) antagonists have been proposed as novel therapeutic agents to combat bacterial infections. We previously reported that the secondary metabolite 3-methyl-<i>N</i>-(2&#8242;-phenylethyl)-butyramide, produced by a marine bacterium identified as <i>Halobacillus</i> <i>salinus</i>, inhibits QS controlled phenotypes in multiple Gram-negative reporter strains. Here we report that <i>N</i>-phenethyl hexanamide, a structurally-related compound produced by the marine bacterium <i>Vibrio</i> <i>neptunius</i>, similarly demonstrates QS inhibitory properties. To more fully explore structure&#8722;activity relationships within this new class of QS inhibitors, a panel of twenty analogs was synthesized and biologically evaluated. Several compounds were identified with increased attenuation of QS-regulated phenotypes, most notably <i>N</i>-(4-fluorophenyl)-3-phenylpropanamide against the marine pathogen <i>Vibrio harveyi</i> (IC₅₀ = 1.1 &#181;M). These findings support the opportunity to further develop substituted phenethylamides as QS inhibitors.