Quorum Sensing and NF-κB Inhibition of Synthetic Coumaperine Derivatives from <i>Piper nigrum</i>

• Main Authors: Yael Kadosh, Subramani Muthuraman, Karin Yaniv, Yifat Baruch, Jacob Gopas, Ariel Kushmaro, Rajendran Saravana Kumar
• Format: Article
• Language: English
• Published: MDPI AG 2021-04-01
• Series: Molecules
• Subjects: quorum sensing; antibacterial; NF-kB; <i>Piper nigrum</i>; coumaperine; plant natural-based compounds
• Online Access: https://www.mdpi.com/1420-3049/26/8/2293

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 (<i>Piper nigrum</i>), 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.