JP3840536B2 - New chalcone derivatives - Google Patents
New chalcone derivatives Download PDFInfo
- Publication number
- JP3840536B2 JP3840536B2 JP2001220775A JP2001220775A JP3840536B2 JP 3840536 B2 JP3840536 B2 JP 3840536B2 JP 2001220775 A JP2001220775 A JP 2001220775A JP 2001220775 A JP2001220775 A JP 2001220775A JP 3840536 B2 JP3840536 B2 JP 3840536B2
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- Prior art keywords
- chalcone derivative
- present
- novel
- antimutagenic
- chalcone
- Prior art date
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Links
- 150000001788 chalcone derivatives Chemical class 0.000 title description 7
- GVSPXQVUXHMUMA-MDWZMJQESA-N (e)-3-(3,5-ditert-butyl-4-hydroxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one Chemical compound C1=CC(OC)=CC=C1C(=O)\C=C\C1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 GVSPXQVUXHMUMA-MDWZMJQESA-N 0.000 claims description 24
- 239000000126 substance Substances 0.000 claims description 16
- 239000003960 organic solvent Substances 0.000 claims description 5
- 239000003112 inhibitor Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 230000000711 cancerogenic effect Effects 0.000 claims description 3
- 231100000315 carcinogenic Toxicity 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 241000256111 Aedes <genus> Species 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 230000002790 anti-mutagenic effect Effects 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 10
- 241000196324 Embryophyta Species 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 239000003814 drug Substances 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 239000003471 mutagenic agent Substances 0.000 description 5
- 231100000707 mutagenic chemical Toxicity 0.000 description 5
- 238000012360 testing method Methods 0.000 description 4
- 239000002537 cosmetic Substances 0.000 description 3
- -1 ethyl ether Chemical compound 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 3
- NZRLNLVUUYPAGG-UHFFFAOYSA-N 1,4‐dimethyl‐2H‐pyrido[4,3‐b]indol‐3‐amine Chemical compound C1=CC=C2C3=C(C)NC(N)=C(C)C3=NC2=C1 NZRLNLVUUYPAGG-UHFFFAOYSA-N 0.000 description 2
- ARZWATDYIYAUTA-UHFFFAOYSA-N 3-methyl-3H-imidazo[4,5-f]quinolin-2-amine Chemical compound C1=CC2=NC=CC=C2C2=C1N(C)C(N)=N2 ARZWATDYIYAUTA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- UQVKZNNCIHJZLS-UHFFFAOYSA-N PhIP Chemical compound C1=C2N(C)C(N)=NC2=NC=C1C1=CC=CC=C1 UQVKZNNCIHJZLS-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 241000234299 Zingiberaceae Species 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 150000001789 chalcones Chemical class 0.000 description 2
- 235000005513 chalcones Nutrition 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 125000004585 polycyclic heterocycle group Chemical group 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LYDZCXVWCFJAKQ-UHFFFAOYSA-N (2,6-dihydroxy-4-methoxyphenyl)-[3-methyl-2-(3-methylbut-2-enyl)-6-phenylcyclohex-3-en-1-yl]methanone Chemical compound OC1=CC(OC)=CC(O)=C1C(=O)C1C(C=2C=CC=CC=2)CC=C(C)C1CC=C(C)C LYDZCXVWCFJAKQ-UHFFFAOYSA-N 0.000 description 1
- LKKMLIBUAXYLOY-UHFFFAOYSA-N 3-Amino-1-methyl-5H-pyrido[4,3-b]indole Chemical compound N1C2=CC=CC=C2C2=C1C=C(N)N=C2C LKKMLIBUAXYLOY-UHFFFAOYSA-N 0.000 description 1
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 1
- 238000010953 Ames test Methods 0.000 description 1
- 231100000039 Ames test Toxicity 0.000 description 1
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 241000876833 Emberizinae Species 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 241000245165 Rhododendron ponticum Species 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 230000001767 chemoprotection Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 125000002350 geranyl group Chemical group [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000006481 glucose medium Substances 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 239000000077 insect repellent Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical group C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Images
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【０００１】
【発明の属する技術分野】
本発明は、新規カルコン誘導体、その製造方法並びに用途に関するものである。本発明に係る新規カルコン誘導体は、優れた抗変異原作用を有しており、飲食品、化粧品、医薬品等に添加して用いる発ガン抑制剤として有用である。
【０００２】
【従来の技術】
カルコン類は、広く植物界に分布し、古くから知られている一群の化合物であり、ほ乳類に対して抗ガン、ガンの化学防御活性、抗菌活性等の働きを持つことが知られている (Dimmock, J. R. et al., Curr. Med. Chem., 1999, 6, 1125-1149)。
一方、従来より、オオバンガジュツを含むショウガ科植物が抗菌防虫作用、鎮痛解熱効果並びに発汗促進効果等の薬理作用を示すことが知られており、該作用を有する物質も単離されている(Panthong, A.et al., J. Ethnopharmacol., 1986, 18, 213-228; Panthong, A.et al., J. Ethnopharmacol., 1991, 31, 121-156)。
しかしながら、上記の植物が抗変異原作用を有することについては、これまで報告がなされていない。
【０００３】
【発明が解決しようとする課題】
本発明の目的は、オオバンガジュツを含むショウガ科植物が有する新規な薬理作用、特に抗変異原作用について究明することである。
【０００４】
【課題を解決するための手段】
そこで、本発明者らは、これら植物の薬効成分を検索する目的で、オオバンガジュツからカルコン誘導体を単離取得し、鋭意研究を行ってきた。
その結果、当該カルコン誘導体が文献未載の新規物質であることを見出し、その化学構造を究明し、更に当該物質が抗変異原作用、特に複素多環式芳香族に属する変異原物質に対する抗変異原作用を有することを確認して、本発明の完成に至ったものである。
【０００５】
請求項１に記載の発明は、下記の化学式（Ｉ）で示されるカルコン誘導体である。
【化２】
請求項２に記載の発明は、オオバンガジュツから有機溶媒で抽出することを特徴とする請求項１記載のカルコン誘導体の製造方法である。
【０００７】
請求項３に記載の発明は、請求項１記載のカルコン誘導体を有効成分として含有する発ガン抑制剤である。
【０００８】
【発明の実施の形態】
請求項１に係る本発明のカルコン誘導体は、上記の化学式（Ｉ）で示される物質である。
カルコン類にゲラニル基が付加した構造を有する化合物は、これまでにいくつか報告されており、パンデュラティンＡ（2,6-dihydroxy-4-methoxyphenyl-[(1RS, 2SR, 6RS)-3-methyl-2-(3-methylbut-2-enyl)-6-phenyl-cyclohex-3-enyl]methanone)等が公知である（Tuntiwachwuttikul, P. et al., Aust. J. Chem., 1984, 37, 449-453)。
しかしながら、カルコン骨格のＡ環に３カ所の水酸基を有する誘導体は報告がなく、本発明をもって最初とするものである。
【０００９】
本発明に係る新規カルコン誘導体は、下記表１に示される理化学的性質を有している。
【００１０】
【表１】
表１ カルコン誘導体の理化学的性質
以上のような理化学的性質及びその他の研究から、本発明に係る新規カルコ ン誘導体は、2,4,6-trihydroxyphenyl-[(1R*, 2S*, 6R*)-3-methyl-2-(3-meth ylbut-2-enyl)-6-phenyl-cyclohex-3-enyl]methanoneであることが判明した。 その化学構造式は、前記の式（Ｉ）に示される。
【００１２】
本発明に係る新規カルコン誘導体は、熱帯・亜熱帯アジア地域において食用、医薬用として広く栽培されているオオバンガジュツより得ることが可能である。その取得方法の一例を以下に示す。
本発明に係る新規カルコン誘導体は、オオバンガジュツから有機溶媒による抽出処理によって得ることができる。ここで、有機溶媒としては、メチルアルコール、エチルアルコール等のアルコール類、エチルエーテル等のエーテル類などが好適に用いられる。有機溶媒による抽出は、常温下に行えばよい。
抽出後、必要に応じて精製処理を行うことによって、精製されたカルコン誘導体を得ることができる。精製処理は、常法により行えばよく、例えばジエチルエーテル：水の分配処理、カラムクロマトグラフィー等各種のクロマトグラフィー等や植物成分の分離、抽出に利用される公知の方法を単独であるいは適宜組み合わせて行うことができる。このようにして得られた粗抽出物は、必要に応じて常法に従って更に精製することができる。
【００１３】
本発明に係るカルコン誘導体は、後記する実施例からも明らかなように、エームス試験法による複素環式多環芳香族に属する変異原物質に対する抗変異原作用を有しており、他の植物由来抗変異原物質に比較して強い作用が認められる。
当該物質の原料であるオオバンガジュツは、長年に亘り人類が食用及び薬用として用いてきた植物であり、安全で、急性毒性は認められない。
【００１４】
このように、本発明に係る新規カルコン誘導体は、卓越した抗変異原作用を示し、且つ安全性も極めて高いので、発ガン抑制剤として飲食品、化粧品、医薬などに添加して使用することができる。
【００１５】
【実施例】
以下に、オオバンガジュツ根茎部を原料とした、本発明に係る新規カルコン誘導体の取得方法並びに当該物質の抗変異原作用に関する実施例などを示すが、本発明はこれらに限定されるものではない。
【００１６】
実施例１
カルコン誘導体の取得
オオバンガジュツ根茎部１ｋｇを３Ｌのメタノールと共にホモジェナイズし、２４時間室温で浸漬することにより抽出し、抽出液をロータリーエバポレータを用いて粘稠なシロップ状になるまで濃縮した。
これをジエチルエーテル：水＝５：２により分配した。エーテル層を分け取って濃縮し、メタノール５００ｍＬに溶解させた。これを逆相カラムクロマトグラフィー(Wakogel40C18)により分画し、得られた画分をTSKgel ODS80Tsカラムを接続した高速液体クロマトグラフィーにより更に分画した。
【００１７】
ここで得られた画分を濃縮し、メタノール中で再結晶させて純粋な化合物を得た。この化合物について質量分析、ＵＶ吸収スペクトル分析並びにプロトン及びカーボン核磁気共鳴分析により化学構造を決定した（図１−４）。
【００１８】
実施例２
抗変異原作用の測定
（１）方法
約４×１０7 個の細胞を含むサルモネラ・ティフィムリウム TA98 株の培養液に複素多環式芳香族の変異原（５０ｎｇのTrp-P-1 または２０ｎｇのTrp-P-2 または２５０ｎｇのPhIP) 及び３．０ｎｍｏｌのチトクロムP450を含むラット肝より調製したＳ９画分を加え、2,4,6-trihydroxyphenyl-[(1R*, 2S*, 6R*)-3-methyl-2-(3-methylbut-2-enyl)-6-phenyl-cyclohex-3-enyl]methanone（０．１μｍｏｌ）のメタノール溶液と共に、２０分間加温した後、最少グルコース培地で２日間培養した。
この培養で出現した復帰変異コロニー数を計数した。被検試料無添加の系をコントロール（０％抑制）とし、Trp-P-1 を添加しなかった系をバックグラウンド（１００％抑制）として、突然変異抑制率を計算した（表２）。
【００１９】
【表２】
表２ 新規カルコン誘導体の抗変異原作用
（２）試験結果
以上の試験結果より明らかなように、新規カルコン誘導体は、強力な抗変異原作用を有する。この作用のED50（５０％抑制濃度）は、約１２．７ｎｍｏｌ／ｔｅｓｔである。この値は、種々のカルコン誘導体類縁化合物のＩＱ (2-amino-3-methylimidazo[4,5-f]quinoline)に対するED50と比較して、同程度か又は数倍強力である（表３、Edenharder et al., Mutat. Res., 287, 261-274より引用）。
【００２１】
【表３】
表３ カルコン誘導体類縁化合物のIQ (2-amino-3-methylimidazo
[4,5-f]quinoline)に対する抗変異原作用
【発明の効果】
本発明によれば、新規カルコン誘導体、2,4,6-trihydroxyphenyl-[(1R*, 2S*,6R*)-3-methyl-2-(3-methylbut-2-enyl)-6-phenyl-cyclohex-3-enyl]methanone とその製造方法並びに用途が提供される。
この物質は、変異原物質、特に複素多環式芳香族に属する変異原物質に対する抗変異原作用を有しており、発ガン抑制作用を目的して食品、化粧品、医薬品等に添加し、広く利用することができるものである。
また、本発明によって当該新規カルコン誘導体の化学構造が明らかにされたので、これを化学修飾したり、各種の改変を加えることにより、新規な配糖体、新規なアグリコン等の従来未知の化合物を更に得ることも大いに期待される。
【図面の簡単な説明】
【図１】 本発明に係る化合物の質量スペクトルを示す。
【図２】 本発明に係る化合物の紫外線吸収スペクトルを示す。
【図３】 本発明に係る化合物のプロトン核磁気共鳴スペクトルを示す。
【図４】 本発明に係る化合物のカーボン核磁気共鳴スペクトルを示す。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a novel chalcone derivative, its production method and use. The novel chalcone derivative according to the present invention has an excellent antimutagenic activity and is useful as a carcinogenic inhibitor used by being added to foods, drinks, cosmetics, pharmaceuticals and the like.
[0002]
[Prior art]
Chalcones are a group of compounds that have been widely distributed in the plant kingdom and have been known for a long time, and are known to have anticancer, chemoprotective and antimicrobial activities against mammals ( Dimmock, JR et al., Curr. Med. Chem., 1999, 6, 1125-1149).
On the other hand, it has been conventionally known that ginger family plants including columbum edibles exhibit pharmacological actions such as antibacterial insect repellent action, analgesic antipyretic effect and sweat promoting effect, and substances having such action have also been isolated (Panthong , A. et al., J. Ethnopharmacol., 1986, 18, 213-228; Panthong, A. et al., J. Ethnopharmacol., 1991, 31, 121-156).
However, there has been no report so far on the above plant having an antimutagenic effect.
[0003]
[Problems to be solved by the invention]
The object of the present invention is to investigate a novel pharmacological action, particularly an antimutagenic action, possessed by a ginger family plant that includes covetus.
[0004]
[Means for Solving the Problems]
Accordingly, the present inventors have conducted earnest research by isolating and obtaining a chalcone derivative from the red bunting for the purpose of searching for medicinal components of these plants.
As a result, the chalcone derivative was found to be a novel substance not described in the literature, its chemical structure was investigated, and further, the substance was antimutagenic, particularly antimutagenic against mutagens belonging to heteropolycyclic aromatics. After confirming that it has the original action, the present invention has been completed.
[0005]
The invention according to
[Chemical 2]
The invention according to claim 2 is the method for producing a chalcone derivative according to
[0007]
The invention described in claim 3 is a carcinogenic inhibitor containing the chalcone derivative according to
[0008]
DETAILED DESCRIPTION OF THE INVENTION
The chalcone derivative of the present invention according to
Several compounds having a structure in which a geranyl group is added to chalcones have been reported so far. Pandulatine A (2,6-dihydroxy-4-methoxyphenyl-[(1RS, 2SR, 6RS) -3- methyl-2- (3-methylbut-2-enyl) -6-phenyl-cyclohex-3-enyl] methanone) and the like are known (Tuntiwachwuttikul, P. et al., Aust. J. Chem., 1984, 37 , 449-453).
However, there is no report of a derivative having three hydroxyl groups in the A ring of the chalcone skeleton, and this is the first of the present invention.
[0009]
The novel chalcone derivative according to the present invention has the physicochemical properties shown in Table 1 below.
[0010]
[Table 1]
Table 1 Physicochemical properties of chalcone derivatives
From the above physicochemical properties and other studies, the novel chalcone derivative according to the present invention is 2,4,6-trihydroxyphenyl-[(1R *, 2S *, 6R *)-3-methyl-2- ( It was found to be 3-methylyl-2-enyl) -6-phenyl-cyclohex-3-enyl] methanone. Its chemical structural formula is shown in the above formula (I).
[0012]
The novel chalcone derivative according to the present invention can be obtained from columbane cultivated widely for food and medicine in tropical and subtropical Asian regions. An example of the acquisition method is shown below.
The novel chalcone derivative according to the present invention can be obtained from an agarite by extraction with an organic solvent. Here, as the organic solvent, alcohols such as methyl alcohol and ethyl alcohol, ethers such as ethyl ether, and the like are preferably used. Extraction with an organic solvent may be performed at room temperature.
A purified chalcone derivative can be obtained by performing a purification treatment as necessary after the extraction. The purification treatment may be carried out by a conventional method, for example, diethyl ether: water partitioning treatment, various chromatographies such as column chromatography, etc., and known methods used for separation and extraction of plant components alone or in combination as appropriate. It can be carried out. The crude extract thus obtained can be further purified according to a conventional method, if necessary.
[0013]
The chalcone derivative according to the present invention has an antimutagenic effect on mutagens belonging to heterocyclic polycyclic aromatics by the Ames test method, as is apparent from the examples described later, and is derived from other plants. Strong effect compared to antimutagenic substances.
Oban ganju, the raw material of the substance, is a plant that human beings have used for food and medicine for many years and is safe and has no acute toxicity.
[0014]
Thus, since the novel chalcone derivative according to the present invention exhibits an excellent antimutagenic action and is extremely safe, it can be used as a carcinogenesis inhibitor by adding it to foods, drinks, cosmetics, medicines and the like. it can.
[0015]
【Example】
Examples of the method for obtaining a novel chalcone derivative according to the present invention and the antimutagenic action of the substance using raw rhizomes as raw materials are shown below, but the present invention is not limited thereto.
[0016]
Example 1
Obtaining a
This was partitioned with diethyl ether: water = 5: 2. The ether layer was separated and concentrated, and dissolved in 500 mL of methanol. This was fractionated by reverse phase column chromatography (Wakogel 40C18), and the obtained fraction was further fractionated by high performance liquid chromatography connected to a TSKgel ODS80Ts column.
[0017]
The fraction obtained here was concentrated and recrystallized in methanol to obtain a pure compound. The chemical structure of this compound was determined by mass spectrometry, UV absorption spectrum analysis, and proton and carbon nuclear magnetic resonance analysis (FIGS. 1-4).
[0018]
Example 2
Measurement of anti-mutagenic activity (1) Method Heteropolycyclic aromatic mutagen (50 ng Trp-P-1 or 20 ng) was added to the culture solution of Salmonella typhimurium TA98 strain containing about 4 × 10 7 cells. S9 fraction prepared from rat liver containing Trp-P-2 or 250 ng of PhIP) and 3.0 nmol of cytochrome P450, and 2,4,6-trihydroxyphenyl-[(1R *, 2S *, 6R *) After warming for 20 minutes with a methanol solution of -3-methyl-2- (3-methylbut-2-enyl) -6-phenyl-cyclohex-3-enyl] methanone (0.1 μmol), 2 in a minimal glucose medium Cultured for days.
The number of revertant colonies that appeared in this culture was counted. Mutation inhibition rates were calculated with the system without the test sample added as a control (0% inhibition) and the system without Trp-P-1 added as the background (100% inhibition) (Table 2).
[0019]
[Table 2]
Table 2 Antimutagenic effects of new chalcone derivatives
(2) Test results As is clear from the above test results, the novel chalcone derivative has a strong antimutagenic effect. The ED 50 (50% inhibitory concentration) of this action is about 12.7 nmol / test. This value is comparable or several times more potent compared to the ED 50 for IQ (2-amino-3-methylimidazo [4,5-f] quinoline) of various chalcone derivative analogs (Table 3, (Quoted from Edenharder et al., Mutat. Res., 287, 261-274).
[0021]
[Table 3]
Table 3 IQ (2-amino-3-methylimidazo) of related compounds of chalcone derivatives
Antimutagenic effect on [4,5-f] quinoline)
【The invention's effect】
According to the present invention, a novel chalcone derivative, 2,4,6-trihydroxyphenyl-[(1R *, 2S *, 6R *)-3-methyl-2- (3-methylbut-2-enyl) -6-phenyl- Cyclohex-3-enyl] methanone and methods for its production and use are provided.
This substance has antimutagenic action against mutagens, especially mutagens belonging to heteropolycyclic aromatics, and is widely added to foods, cosmetics, pharmaceuticals, etc. for the purpose of inhibiting carcinogenesis. It can be used.
In addition, since the chemical structure of the novel chalcone derivative has been clarified by the present invention, a previously unknown compound such as a novel glycoside or a novel aglycone can be obtained by chemically modifying this or by making various modifications. It is also highly anticipated to get more.
[Brief description of the drawings]
FIG. 1 shows a mass spectrum of a compound according to the present invention.
FIG. 2 shows an ultraviolet absorption spectrum of the compound according to the present invention.
FIG. 3 shows a proton nuclear magnetic resonance spectrum of the compound according to the present invention.
FIG. 4 shows a carbon nuclear magnetic resonance spectrum of the compound according to the present invention.
Claims (3)
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