Quorum Sensing and NF-κB Inhibition of Synthetic Coumaperine Derivatives from Piper nigrum

Bacterial communication, termed Quorum Sensing (QS), is a promising target for virulence attenuation and the treatment of Bacterial infections. Infections cause inflammation, a process regulated by a number of cellular factors, including the transcription Nuclear Factor kappa B (NF-κB); this factor is found to be upregulated in many inflammatory diseases, including those induced by Bacterial infection. In this study, we tested 32 synthetic derivatives of coumaperine (CP), a known natural compound found in pepper (Piper nigrum), for Quorum Sensing Inhibition (QSI) and NF-κB inhibitory activities. Of the compounds tested, seven were found to have high QSI activity, three inhibited Bacterial growth and five inhibited NF-κB. In addition, some of the CP compounds were active in more than one test. For example, compounds CP-286, CP-215 and CP-158 were not cytotoxic, inhibited NF-κB activation and QS but did not show Antibacterial activity. CP-154 inhibited QS, decreased NF-κB activation and inhibited Bacterial growth. Our results indicate that these synthetic molecules may provide a basis for further development of novel therapeutic agents against Bacterial infections.

NF-kB; Piper nigrum; amide alkaloids; antibacterial; coumaperine; plant natural-based compounds; quorum sensing.