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.
Tsukamoto
Sachiko
S
Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan.
Tomise
Kyoko
K
Miyakawa
Keiko
K
Cha
Bae-Cheon
BC
Abe
Takamasa
T
Hamada
Toshiyuki
T
Hirota
Hiroshi
H
Ohta
Tomihisa
T
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