Piperine analogs as potent Staphylococcus aureus NorA efflux pump inhibitors

Piperine analogs derived from piperine have been shown to possess potent efflux pump inhibitory activity against NorA system of Staphylococcus aureus having better potentiation activity than known EPIs. Based on our recent findings that piperine is a potent Staphylococcus aureus NorA efflux pump inhibitor (EPI), 38 piperine analogs were synthesized and bioevaluated for their EPI activity. Twenty-five of them were found active with potentiating activity equivalent or more than known EPIs like reserpine, carsonic acid and verapamil. The inhibitory mechanism of the compounds was confirmed by efflux inhibition assay using ethidium bromide as NorA substrate. The present communication describes the synthesis, bioevaluation and structure related activity of these efflux pump inhibitors.