Pyridines with adamantane fragments and their 1,2,4-triazine analogues as anti-quorum-sensing agents, synthesis and molecular docking.

Due to the increasing resistance of bacterial strains to conventional antibiotics, there is an urgent need to develop alternative antibacterial agents for the treatment of diseases caused by drug-resistant bacteria. A promising group of such agents is quorum sensing (QS) inhibitors. QS is an interbacterial communication process that regulates the formation of protective biofilms by bacterial colonies, which significantly reduces treatment efficacy. In this study, we designed and synthesized pyridines bearing adamantane fragments through their 1,2,4-triazine analogues and evaluated their potential anti-QS activity using molecular docking followed by an analysis of non-covalent interaction profiles. Lead compounds 2c, 3a, and 2a exhibited potential binding activity against the LsrR protein of E. coli and the LasR and PqsE proteins of P. aeruginosa, respectively. These compounds demonstrated equal or higher binding affinity to the target proteins compared to their native ligands: D8P (a synthetic LsrR inhibitor), 3O-C12-HSL (a natural LasR agonist), and C4-HSL (a natural PqsE agonist). The obtained results indicate the potential of this class of compounds for further development as QS inhibitors.