Effect of Chain Length on the Antimicrobial Properties of Dialkylresorcinols

Dialkylresorcinols (DARs) are naturally occurring compounds produced in several species of the Photorhabdus and Pseudomonas bacterial genera, which are involved in modulating quorum-sensing in the producing organisms, as well as possessing significant antimicrobial properties. A range of dialkylresorcinols were synthesized, systematically varying the chain-lengths of the C-2 and C-5 alkyl chains, and the antimicrobial properties of the products assessed. Against two Staphylococcus test strains, medium-length alkyl chains (5-7 carbons) in both positions proved optimum for high antibiotic activity, with several derivatives displaying low micromolar activity. Activity against other test organisms was very different, with 2-hexylresorcinol (11) displaying the highest potency against Escherichia coli, Pseudomonas syringae, and Xanthomonas campestris test strains; its structure likely enables efficient membrane interaction while maintaining bioavailability.