Design, synthesis, and biological evaluation of benzoheterocyclic sulfoxide derivatives as quorum sensing inhibitors in Pseudomonas aeruginosa

Six series of benzoheterocyclic sulfoxide derivatives were designed and synthesised as Pseudomonas aeruginosa (P. aeruginosa) quorum sensing inhibitors in this paper. We experimentally demonstrated that 6b significantly inhibited the formation of P. aeruginosa PAO1 biofilm without affecting the growth. Further mechanistic studies showed that 6b affected the luminescence of quorum sensing reported strain PAO1-lasB-gfp and the production of P. aeruginosa PAO1 elastase virulence factor which was regulated by las system. These experimental results indicate that 6b acts as a quorum sensing inhibitor mainly through the las system. Furthermore, silico molecular docking studies demonstrated that 6b and the P. aeruginosa quorum sensing receptor LasR were molecularly bound via hydrogen bonding interactions. Preliminary structure-activity relationship and docking studies illustrated that 6b shows great promise as anti-biofilm compounds for further studies in order to solve the problem of microbial resistance in future.

Automated summary

In this paper, six series of benzoheterocyclic sulfoxide derivatives were designed and synthesised as Pseudomonas aeruginosa quorum sensing inhibitors. The experimental results showed that 6b significantly inhibited the formation of P. aeruginosa PAO1 biofilm without affecting the growth. Further mechanistic studies revealed that 6b mainly acted as a quorum sensing inhibitor through the las system. Silico molecular docking studies demonstrated the molecular binding between 6b and the P. aeruginosa quorum sensing receptor LasR via hydrogen bonding interactions. The structure-activity relationship and docking studies suggested the potential of 6b as anti-biofilm compounds for further studies on microbial resistance.