Design, Synthesis, Biological Evaluation, and In Silico Study of N-(Pyrazin-2-yl)Alkyl/Aryl Amide Derivatives as...

This research develops novel quorum sensing inhibitors (QSIs) that function as anti-biofilm agents and reduce quorum sensing (QS) to effectively combat Pseudomonas aeruginosa. N-(Pyrazin-2-yl)alkyl/aryl amide derivatives (3a-k) and (5a-j) were designed and synthesized in this study. Further, QS inhibition activity of N-(pyrazin-2-yl)alkyl/aryl amide derivatives (3a-k) and (5a-j) was compared to dimethyl sulfoxide (DMSO) (5%) (2.33 ± 0.05), which was used as a reference for QSIs. The anti-QS activity of N-(pyrazin-2-yl)alkyl/aryl amide derivatives 3b, 3d, 3e, 3f, 3g, 3h, 5a, and 5g was found to be higher (zone of inhibition, 10 ± 0.33 to 15 ± 0.33). The binding affinity values between -9.17 and -6.21 kcal/mol were found to be moderate to good in subsequent molecular docking experiments. Furthermore, the stability of the protein and ligand complex of compounds 3f and 3g was better understood using molecular dynamics simulation. Utilizing the in silico approach, the physicochemical characteristics and binding strategy of these developed compounds were examined. Overall study findings indicated that N-(pyrazin-2-yl)alkyl/aryl amide derivatives (3a-k) and (5a-j) might be useful for the development of novel QSI.