Identification of 3-nitrophenol ester derivatives as novel quorum-sensing inhibitors of Pseudomonas aeruginosa

In this study, we report a series of 3-nitrophenol ester derivatives as promising quorum-sensing (QS) in-hibitors via Structure-based Virtual Screening and structural optimization. Spectroscopic and analytical data were used to validate all synthesized targets. All the compounds were assessed for in vitro LasR in-hibition activity. 3-Nitrophenol ester 1b was identified as the most promising candidate, which showed potent LasR inhibition activity (IC50, 5.94 mu g/ml), low cytotoxicity (CC50 > 10 0 0 mu g/ml) and no signif-icantly bactericidal activity. Molecular docking study suggested that 1b with higher crash score value formed three intermolecular hydrogen bonds with the residues. In addition, 1b was proved to show sig-nificantly virulence inhibition against P. aeruginosa in vitro and in vivo. The whole transcriptome analysis of 1b also suggested that QS-related genes were inhibited. Taken together, compound 1b is a novel and promising QS inhibitor, which is worth for in-depth study.(c) 2022 Elsevier B.V. All rights reserved.