Design, synthesis and activity evaluation of dithiocarbamate-based L-homoserine lactone derivatives as Gram-negative bacteria quorum sensing inhibitors

Pseudomonas aeruginosa (P. aeruginosa) is an important Gram-negative opportunistic pathogen that uses quorum sensing to regulate its virulence and biofilm development, which contributes to its pathogenicity and drug resistance. As a result, focusing on the virulence and pathogenicity of P. aeruginosa through quorum sensing (QS) is considered a possible target for anti-infective therapy. In this work, we discovered new quorum-sensing inhibitors derived from the structural modification of the dithiocarbamate-based l-homoserine lactone derivatives library and the target compound (10p) demonstrated significant inhibitory activity against PAO1 biofilm (inhibition rate: 86.76 %), pyocyanin (68.05 %), rhamnolipid (34.56 %), LasA protease (61.01 %) and a low inhibitory on elastase production (6.59 %) at 60 μM. Moreover, compound 10p effectively attenuated P. aeruginosa motility, such as swimming (42.85 %) and swarming (72 %), and demonstrated no toxicity in vitro. The result indicates that compound 10p may serve as a promising new antibacterial synergist option for treating P. aeruginosa infections.