CYP3A4 inhibitory activity of new bisalkaloids, dipiperamides D and E, and cognates from white pepper

Abstract

Two new bisalkaloids, dipiperamides D and E, were isolated as inhibitors of a drug metabolizing enzyme cytochrome P450 (CYP) 3A4 from the white pepper, Piper nigrum. Their structures were elucidated by spectroscopic methods. Dipiperamides D and E showed potent CYP3A4 inhibition with IC(50) values of 0.79 and 0.12 microM, respectively, and other metabolites from the pepper were moderately active or inactive.