Alkamides from Piper nigrum L. and their inhibitory activity against human liver microsomal cytochrome P450 2D6 (CYP2D6)

Abstract

Drug–herb interaction through inhibition of cytochrome P450 alters the pharmacological response and/or toxicities of drug used concomitantly. In our screening, Piper nigrum L. was observed to inhibit cytochrome P450 2D6 (CYP2D6) in human liver microsomes. Thus, the MeOH extract of this plant was investigated for their chemical constituents and 19 alkamides including a new pipercyclobutanamide were isolated. Their structures were elucidated on the basis of spectroscopic analyses. The isolated compounds were tested for their inhibition on human liver microsomal dextromethorphan O-demethylation activity, a selective marker for CYP2D6, and pipercyclobutanamide A (17) showed the most potent inhibition with an IC 50 value of 0.34 μM. The result demonstrated the potential of drug–alkamides interaction on concomitant consume of white pepper with the drugs being metabolized by CYP2D6.

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