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

Abstract

The efficient synthesis of novel 2,2-dimethyl-chroman-6-yl pentadienoic acid amides (<strong>7a-e</strong>) 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 <strong>6 </strong>with various aromatic amines. All the synthesized piperine analogs were bioevaluated for their potential as inhibitors of multidrug efflux pump NorA overexpressing <em>Staphylococcus aureus</em> SA 1199B. Out of all the prepared analogs, 5-(2,2-dimethyl-chroman-6-yl)-4-methyl-penta-2,4-dienoic acid ethyl ester <strong>5</strong> and 5-(2,2-Dimethyl-chroman-6-yl)-4-methyl-2E,4E-pentadienoic acid pyrrolidide <strong>7d </strong>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 <em>Staphylococcus aureus</em> isolates. Structures of the synthesized compounds have been elucidated on the basis of spectral data (IR, ¹H NMR and Mass analysis).