Cytochrome P450 3A4 inhibitory constituents of the wood of Taxus yunnanensis

Yasuhiro Tezuka; Kouhei Morikawa; Feng Li; Lidyawati Auw; Suresh Awale; Takahiro Nobukawa; Shigetoshi Kadota

doi:10.1021/np100665j

Cytochrome P450 3A4 inhibitory constituents of the wood of Taxus yunnanensis

J Nat Prod. 2011 Jan 28;74(1):102-5. doi: 10.1021/np100665j. Epub 2010 Dec 7.

Authors

Yasuhiro Tezuka¹, Kouhei Morikawa, Feng Li, Lidyawati Auw, Suresh Awale, Takahiro Nobukawa, Shigetoshi Kadota

Affiliation

¹ Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. tezuka@inm.u-toyama.ac.jp

PMID: 21138310
DOI: 10.1021/np100665j

Abstract

From the aqueous extract of the wood of Taxus yunnanensis, which showed cytochrome P450 3A4 (CYP3A4) inhibition, a new isoflavan [(3S,4R)-4'-hydroxy-6,3'-dimethoxyisoflavan-4-ol (1)], a new degraded lignan [2,3-bis(hydroxymethyl)-7-hydroxy-6-methoxy-1-tetralone (2)], and a new lignan [(7R)-7-hydroxytaxiresinol (3)] were isolated, together with nine known lignans. Among the isolates obtained, α-conidendrin (12) showed strong CYP3A4 inhibition with an IC(50) value of 0.2 μM.

MeSH terms

Antineoplastic Agents, Phytogenic / chemistry
Antineoplastic Agents, Phytogenic / isolation & purification*
Antineoplastic Agents, Phytogenic / pharmacology*
Antioxidants / chemistry
Antioxidants / isolation & purification*
Antioxidants / pharmacology*
Biphenyl Compounds / pharmacology
Colletotrichum / chemistry*
Cytochrome P-450 CYP3A
Cytochrome P-450 CYP3A Inhibitors*
Drug Screening Assays, Antitumor
Free Radical Scavengers / chemistry
Free Radical Scavengers / isolation & purification*
Free Radical Scavengers / pharmacology*
Furans / chemistry
Furans / isolation & purification*
Furans / pharmacology*
Hep G2 Cells
Humans
Isocoumarins / chemistry
Isocoumarins / isolation & purification*
Isocoumarins / pharmacology*
Isoflavones / chemistry
Isoflavones / isolation & purification*
Isoflavones / pharmacology*
Lignans / chemistry
Lignans / isolation & purification*
Lignans / pharmacology*
Molecular Structure
Nuclear Magnetic Resonance, Biomolecular
Picrates / pharmacology
Taxus / microbiology
Tetrahydronaphthalenes / chemistry
Tetrahydronaphthalenes / isolation & purification*
Tetrahydronaphthalenes / pharmacology*
Wood / chemistry

Substances

(3S,4R)-4'-hydroxy-6,3'-dimethoxyisoflavan-4-ol
(7R)-7-hydroxytaxiresinol
2,3-bis(hydroxymethyl)-7-hydroxy-6-methoxy-1-tetralone
Antineoplastic Agents, Phytogenic
Antioxidants
Biphenyl Compounds
Cytochrome P-450 CYP3A Inhibitors
Free Radical Scavengers
Furans
Isocoumarins
Isoflavones
Lignans
Picrates
Tetrahydronaphthalenes
conidendrin
1,1-diphenyl-2-picrylhydrazyl
Cytochrome P-450 CYP3A
CYP3A4 protein, human