107(P-62) 食品に由来する薬物相互作用物質の化学(ポスター発表の部)

概要

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Increase in bioavailability by simultaneous intake of grapefruit juice has been reported with various medicines widely used clinically including the dihydropyridine calcium channel blockers, cyclosporine, midazolam, triazolam and terfenadine. Increase in the concentration originates in metabolic change by the metabolic enzyme CYP3A4. We have reported the isolation of furanocoumarin (furocoumarin) dimers, paradisin A (GF-I-1, 1) and B (GF-I-4, 2) and C (GF-I-6, 3) as the major active components in grapefruit juice. The presence of the intact paradisins was confirmed in the unprocessed fruit Citrus paradisii. In commercially available grapefruit juice, paradisins localized only in the pale yellow solid (pulp) but not in pulp-free liquid. We have prepared various esters of dihydroxybergamottin (4) and found that the caproate (11) showed exhibited comparable inhibition to paradisin A (1) against CYP3A4. Piperine (19) is known to elevate the serum level of drugs and nutrients by inhibiting the metabolism by CYP3A4. During our research on CYP inhibitors from the diet, it was discovered that an EtOAc extract of white pepper showed more potent activity compared to piperine (19). Bioassay-monitored purification afforded five new alkaloids, dipiperamides A-E (20-24) having high potency of CYP inhibition, IC_<50> 0.18-0.79μM. Structures of those were elucidated by spectroscopic analysis.
天然有機化合物討論会の論文
2002-09-01