論文 - 詳細
| RRC ID | 65014 |
|---|---|
| 著者 | Manse Y, Ninomiya K, Nishi R, Kamei I, Katsuyama Y, Imagawa T, Chaipech S, Muraoka O, Morikawa T. |
| タイトル | Melanogenesis inhibitory activity of a 7-O-9'-linked neolignan from Alpinia galanga fruit. |
| ジャーナル | Bioorg Med Chem |
| Abstract |
An aqueous acetone extract from the fruit of Alpinia galanga (Zingiberaceae) demonstrated inhibitory effects on melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells (IC50=7.3μg/mL). Through bioassay-guided separation of the extract, a new 7-O-9'-linked neolignan, named galanganol D diacetate (1), was isolated along with 16 known compounds including 14 phenylpropanoids (2-15). The structure of 1, including its absolute stereochemistry in the C-7 position, was elucidated by means of extensive NMR analysis and total synthesis. Among the isolates, 1 (IC50=2.5μM), 1'S-1'-acetoxychavicol acetate (2, 5.0μM), and 1'S-1'-acetoxyeugenol acetate (3, 5.6μM) exhibited a relatively potent inhibitory effect without notable cytotoxicity at effective concentrations. The following structural requirements were suggested to enhance the inhibitory activity of phenylpropanoids on melanogenesis: (i) compounds with 4-acetoxy group exhibit higher activity than those with 4-hydroxy group; (ii) 3-methoxy group dose not affect the activity; (iii) acetylation of the 1'-hydroxy moiety enhances the activity; and (iv) phenylpropanoid dimers with the 7-O-9'-linked neolignan skeleton exhibited higher activity than those with the corresponding monomer. Their respective enantiomers [1' (IC50=1.9μM) and 2' (4.5μM)] and racemic mixtures [(±)-1 (2.2μM) and (±)-2 (4.4μM)] were found to exhibit melanogenesis inhibitory activities equivalent to those of the naturally occurring optical active compounds (1 and 2). Furthermore, the active compounds 1-3 inhibited tyrosinase, tyrosine-related protein (TRP)-1, and TRP-2 mRNA expressions, which could be the mechanism of melanogenesis inhibitory activity. |
| 巻・号 | 24(23) |
| ページ | 6215-6224 |
| 公開日 | 2016-12-1 |
| DOI | 10.1016/j.bmc.2016.10.001 |
| PII | S0968-0896(16)30895-1 |
| PMID | 27756508 |
| MeSH | Alpinia / chemistry* Animals Cell Line, Tumor Fruit / chemistry Gene Expression Intramolecular Oxidoreductases / genetics Intramolecular Oxidoreductases / metabolism Lignans / chemistry Lignans / isolation & purification Lignans / pharmacology* Melanins / metabolism* Melanocytes / drug effects* Melanocytes / metabolism Membrane Glycoproteins / genetics Membrane Glycoproteins / metabolism Mice Monophenol Monooxygenase / genetics Monophenol Monooxygenase / metabolism Oxidoreductases / genetics Oxidoreductases / metabolism RNA, Messenger / metabolism Stereoisomerism Theophylline / pharmacology |
| IF | 3.073 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | B16 melanoma 4A5(RCB0557) |