CYP3A4 inhibitory activity of new bisalkaloids, dipiperamides D and E, and cognates from white pepper.
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.
Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan.
Sachiko
S
Tsukamoto
Kyoko
K
Tomise
Keiko
K
Miyakawa
Bae-Cheon
BC
Cha
Takamasa
T
Abe
Toshiyuki
T
Hamada
Hiroshi
H
Hirota
Tomihisa
T
Ohta
D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology; D001682:Biological Availability; D002934:Cinnamates / Q000302:isolation & purification / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D029222:Piper nigrum / Q000737:chemistry*; D010880:Piperidines / Q000302:isolation & purification / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000470:Alkaloids; D002934:Cinnamates; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D010880:Piperidines; C475903:dipiperamide D; C475902:dipiperamide E; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human