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 IC50 values of 0.79 and 0.12 muM. respectively, and other metabolites from the pepper were moderately active or inactive. (C) 2002 Elsevier Science Ltd. All rights, reserved.