Synthesis and Characterization of Piperine Analogs as Potent Staphylococcus aureus NorA Efflux Pump Inhibitors

The efficient synthesis of novel 2,2-dimethyl-chroman-6-yl pentadienoic acid amides (7a-e) as synthetic piperine analogs has been established by the condensation of 5-(2,2-dimethyl-chroman-6-yl)-4-methyl-penta-2,4-dienoic acid 6 with various aromatic amines. All the synthesized piperine analogs were bioevaluated for their potential as inhibitors of multidrug efflux pump NorA overexpressing Staphylococcus aureus SA 1199B. Out of all the prepared analogs, 5-(2,2-dimethyl-chroman-6-yl)-4-methyl-penta-2,4-dienoic acid ethyl ester 5 and 5-(2,2-Dimethyl-chroman-6-yl)-4-methyl-2E,4E-pentadienoic acid pyrrolidide 7d were found promising. The active compounds were also evaluated for their synergistic effect with ciprofloxacin, whose results substantially increase the activity of ciprofloxacin against both Nora overexpressing and wild type Staphylococcus aureus isolates. Structures of the synthesized compounds have been elucidated on the basis of spectral data (IR, 1H NMR and Mass analysis).