Synthesis and study of antibiofilm and antivirulence properties of flavonol analogues generated by palladium catalyzed ligand free Suzuki-Miyaura coupling against PAO1.

The Suzuki-Miyaura coupling is one of the ubiquitous method for the carbon-carbon bond-forming reactions in organic chemistry. Its popularity is due to its ability to undergo extensive coupling reactions to generate a broad range of biaryl motifs in a straightforward manner displaying a high level of functional group tolerance. A convenient and efficient synthetic route to arylate different substituted flavonols through the Suzuki-Miyaura cross-coupling reaction has been explained in this study. The arylated products were acquired by the coupling of a variety of aryl boronic acids with flavonols under Pd(OAc) catalyzed reaction conditions in a ligand-free reaction strategy. Subsequently, the antibiofilm and antivirulence properties of the arylated flavonols against PAO1 were studied thoroughly. The best ligands for quorum sensing proteins LasR, RhlR, and PqsR were identified using molecular docking study. These best fitting ligands were then studied for their impact on gene expression level of by RT-PCR towards quorum sensing genes , , and . The downregulation in the gene expression with the effect of synthesized flavonols endorse the antibiofilm efficiency of the compounds.