1. Melanogenesis inhibitory activity of a 7-O-9′-linked neolignan from Alpinia galanga fruit
- Author
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Saowanee Chaipech, Iyori Kamei, Toshio Morikawa, Yoshiaki Manse, Takahito Imagawa, Ryosuke Nishi, Kiyofumi Ninomiya, Osamu Muraoka, and Yushi Katsuyama
- Subjects
food.ingredient ,Stereochemistry ,Tyrosinase ,Alpinia galanga ,Clinical Biochemistry ,Gene Expression ,Pharmaceutical Science ,01 natural sciences ,Biochemistry ,Lignans ,Mice ,food ,Theophylline ,Cell Line, Tumor ,Drug Discovery ,Animals ,RNA, Messenger ,Cytotoxicity ,Molecular Biology ,Melanins ,Membrane Glycoproteins ,biology ,Phenylpropanoid ,Monophenol Monooxygenase ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Total synthesis ,Stereoisomerism ,biology.organism_classification ,0104 chemical sciences ,Intramolecular Oxidoreductases ,010404 medicinal & biomolecular chemistry ,Acetylation ,Fruit ,Alpinia ,Melanocytes ,Molecular Medicine ,Zingiberaceae ,Enantiomer ,Oxidoreductases - 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 = 7.3 μg/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 = 2.5 μM), 1′S-1′-acetoxychavicol acetate (2, 5.0 μM), and 1′S-1′-acetoxyeugenol acetate (3, 5.6 μM) 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 = 1.9 μM) and 2′ (4.5 μM)] and racemic mixtures [(±)-1 (2.2 μM) and (±)-2 (4.4 μM)] 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.
- Published
- 2016
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