| 概要 |
The inhibitory components on tyrosinase and 5a-reductase from Papua New Guinean (PNG) and Thai woody plants were investigated. First, the inhibitory components of Artocarpus incisus heartwood which sh...owed the strongest inhibitory activity in 23 PNG wood species, their structure-activity relationships and inhibitory mechanism were evaluated. Tyrosinase inhibitory activity-guided fractionation led to the isolation of seven active compounds including two new compounds, 3,2',4'-trihydroxy- 6", 6"-dimethyl-pyrano(3",2":4,5)-trans- stilbene (artocarbene) and 6-(3"-methyl-1"- butenyl)-5,7,2',4'-tetrahydroxyflavone(isoartocarpesin). The structure-activity relation- ships suggested that specific natural or synthesized compounds having4-substituted resorcinol skeleton had potent tyrosinase inhibitory ability. Kinetic studies have indicated that specific compounds having 4-substituted resorcinol skeleton exhibit competitive inhibition of the oxidation of DL-DOPA by mushroom tyrosinase. Second, 5a-reductase inhibitory components from PNG and Thai plants were investigated respectively, and their structure-activity relationships were discussed. The methanol extract of heartwood of A. incisus showed potent 5a-reductase inhibitory activity. Chlorophorin and artocarpin showed more potent inhibitory effects (IC_50=37μM and 85μM, respectively) than did a-linolenic acid, which is known as a naturally occurring potent inhibitor. The inhibitory effects of 17 samples prepared from Thai plants on 5a-reductase activity were examined. The acetone extract of A. incisus leaves showed potent 5a-reductase inhibitory activity. Fractionation guided by 5a-reductase inhibitory test led to the isolation of 2-geranyl-2', 3,4,4'-tetrahydroxydihydrochalcone(IC_50=38μM) and a novel geranylated chalcone, 3'-ger- anyl-2',3,4,4'-tetrahydroxychalcone(IC_50=104μM) from the acetone extract of A. incisus leaves. Structure-activity relationship suggested that the presence of an isoprene-derived sub- stituent (prenyl and geranyl) would enhance 5a-reductase inhibitory effects.
世界の森林面積の約40-50%は熱帯林であり,特に熱帯多雨林は蓄積量も多く,かつ構 成樹種が極めて多種多様であることを特徴としている.これらの樹種の特徴は,化学成分 的に見ると微量成分である抽出成分の量的,質的な大きな変異として現れる.即ち熱帯樹 木抽出成分は有用成分の宝庫であり,興味ある成分が見いだされる可能性が高い.本研究 では,熱帯産樹木抽出成分から,シミやソバカスなどのメラニン色素沈着症の治療薬になり得るチロシナーゼ阻害成分ならびに前立腺肥大症や男性型脱毛症の治療薬として期待される5α-リダクターゼ阻害成分の探索を行った. まず,23種のパプアニューギニア産樹木心材抽出物からのチロシナーゼ阻害成分の探索 を行った.その結果,唯一Artocarpus incisusの心材メタノール抽出物のみが,既知の強力 な阻害剤であるコウジ酸と同等の阻害活性を示した.さらにB16メラノーマ細胞や茶色モ ルモットを用いたメラニン生成抑制試験においても色素の著しい淡色効果を示した.チロ シナーゼ阻害活性を指標に,活性成分の探索を行い,2つの新規化合物(artocarbene, isoartocarpesinと命名)を含む7つの強力なチロシナーゼ阻害成分を単離同定した.構造-活 性相関を検討し,4位置換レゾルシノール構造が強力な阻害活性発現に重要であることを 明らかにした. 次に,パプアニューギニア及びタイ産植物抽出物からの5a-リダクターゼ阻害成分の探 索を行った.その結果,A.incisusの心材及び葉部抽出物が高い阻害活性を示した.活性 成分の探索を行い,新規化合物(3'-geranyl-2',3,4,4'-tetrahydroxychalcone)を含む一連の イソプレノイド置換フラボノイド及びスチルベンを単離,同定した.特に,artocarpin, chlorophorin, 2-geranyl-2',3,4,4'-tetrahydroxydihydrochalcone, 3'-geranyl-2',3,4,4'- tetrahydroxychalconeは既知の天然非ステロイド系阻害剤であるa-リノレン酸より高い阻 害活性を示した.構造-活性相関検討により,イソプレノイド置換基(プレニル基または ゲラニル基)の存在が阻害活性発現に重要であることが判明した.続きを見る
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Mendeley出力
