N-acyl-4-arylaminopiperidines: Design and synthesis of a potential antimicrobial scaffold.

[Display omitted] • 28 N -acylpiperidines were prepared using a three-step and versatile protocol. • Compounds showed antibacterial activity against MRSA and multiresistant K. pneumoniae. • The most active piperidines against K. pneumoniae bore a chlorine atom at the arylamino moiety. • Molecular docking offered insights into the binding mode of the series into the FabI catalytic domain. • The series become an attractive scaffold for the design of more potent antimicrobials. We report a concise synthesis of N -acylated piperidines through a Knoevenagel-Doebner condensation/amide construction/ amination sequence. The design of the piperidines considered the pharmacophoric features found in previously reported inhibitors of FabI, an enzyme implicated in bacterial fatty acid biosynthesis. After the microbiological evaluation at 50 μM, the analogs displayed moderate activity against some pathogens from the ESKAPE group, reaching up to 42 % of growth inhibition for MRSA , 54 % for K. pneumonia e, and 37 % for P. aeruginosa (multiresistant strains). Docking studies demonstrate that almost all of them docked satisfactorily into the catalytic domain of S. aureus FabI, maintaining a similar pose as other reported inhibitors. The results shown herein propose the N -acyl-4-arylaminopiperidines as the basis for the development of more active candidates. [ABSTRACT FROM AUTHOR]