JPH03157379A - Phthalide derivative and cell killing agent of cervical carcinoma cell containing same derivative as active ingredient - Google Patents
Phthalide derivative and cell killing agent of cervical carcinoma cell containing same derivative as active ingredientInfo
- Publication number
- JPH03157379A JPH03157379A JP1295449A JP29544989A JPH03157379A JP H03157379 A JPH03157379 A JP H03157379A JP 1295449 A JP1295449 A JP 1295449A JP 29544989 A JP29544989 A JP 29544989A JP H03157379 A JPH03157379 A JP H03157379A
- Authority
- JP
- Japan
- Prior art keywords
- organic solvent
- derivative
- cell
- phthalide
- killing agent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 230000022534 cell killing Effects 0.000 title claims abstract description 10
- 239000003139 biocide Substances 0.000 title claims abstract description 5
- 125000005506 phthalide group Chemical class 0.000 title claims description 15
- 239000004480 active ingredient Substances 0.000 title claims description 4
- 208000019065 cervical carcinoma Diseases 0.000 title abstract 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 8
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 8
- 201000010881 cervical cancer Diseases 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 15
- 239000003960 organic solvent Substances 0.000 abstract description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 8
- 238000000605 extraction Methods 0.000 abstract description 7
- 239000007788 liquid Substances 0.000 abstract description 4
- 238000001953 recrystallisation Methods 0.000 abstract description 3
- 238000001914 filtration Methods 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract 3
- 240000000588 Hericium erinaceus Species 0.000 abstract 1
- 235000007328 Hericium erinaceus Nutrition 0.000 abstract 1
- 238000004587 chromatography analysis Methods 0.000 abstract 1
- 235000013399 edible fruits Nutrition 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 38
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 230000000445 cytocidal effect Effects 0.000 description 5
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 4
- 150000002137 ergosterols Chemical class 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000005194 fractionation Methods 0.000 description 2
- 238000000622 liquid--liquid extraction Methods 0.000 description 2
- 238000012916 structural analysis Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- KLMRELXLQGRFDO-UHFFFAOYSA-N 5-methoxy-3h-2-benzofuran-1-one Chemical compound COC1=CC=C2C(=O)OCC2=C1 KLMRELXLQGRFDO-UHFFFAOYSA-N 0.000 description 1
- 241000222501 Agaricaceae Species 0.000 description 1
- 241001327634 Agaricus blazei Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 238000002738 Giemsa staining Methods 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 241000222355 Trametes versicolor Species 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 231100000409 cytocidal Toxicity 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000010200 folin Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- -1 loloform Chemical compound 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
Landscapes
- Furan Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
【発明の詳細な説明】
〈産業上の利用分野〉
本発明は、ハリタケ科（Ｈｙｄｎａｃｓａｅ ） 、サ
ンゴハリタケ属（Ｈｅｒｉｃｉｕ■）のキノコであるヤ
マブシタケ（Ｈｅｒｉｃｉｕ＠ｅｒｉｎａｃｅｕｓ）の
子実体中に存在するフタリド誘導体及び該フタリド誘導
体を有効成分とする子宮頚癌細胞の殺細胞剤に関する。Detailed Description of the Invention <Industrial Application Field> The present invention provides phthalide derivatives and The present invention relates to a cell-killing agent for cervical cancer cells containing the phthalide derivative as an active ingredient.
〈従来の技術〉
従来、キノコに含まれる化合物及び該化合物の癌細胞に
対する殺細胞効果について複数の報告がある０例えば、
サルノコシカケ科のキノコであるカワラタケ（Ｐｏｌｙ
ｐｏｒｕｓ ｖｅｒｓｉｃｏｌｏｒ）にはエルゴステロ
ール誘導体が含まれており、該エルゴステロール誘導体
には肝臓癌細胞（Ｈｅｐａｔｏｍａ ｃｅｌｌｓ）に対
する殺細胞効果のあることがテトラヘドロン（Ｔｅｔｒ
ａｈｅｄｒｏｎ）３９ 、２７７９〜２７８５ （１９
８３）に報告されている。またハラタケ科のキノコであ
るヒメマツタケ（Ａｇａｒｉｃｕｓｂｌａｚｅｉ）にも
エルゴステロール誘導体が含まれており、該エルゴステ
ロール誘導体には子宮頚癌細胞に対する殺細胞効果のあ
ることがフィトケミストリ
（Ｐｈｙｔｏｃｈｅｍｉｓｔｒ７） ２７ 、２７７７
〜２７８９ （１９８８）に報告されている。そして同
様のことが特公昭４８−６７６６号公報、特開昭５５−
７１７０２号公報及び特開昭５８−６２１１８号公報等
にも報告されている。<Prior art> There have been several reports on compounds contained in mushrooms and their cytocidal effects on cancer cells, for example,
Poly
porus versicolor) contains an ergosterol derivative, and this ergosterol derivative has been shown to have a cell-killing effect on liver cancer cells (Hepatoma cells).
ahedron) 39, 2779-2785 (19
83). In addition, Agaricus blazei, a mushroom of the Agaricaceae family, also contains ergosterol derivatives, and these ergosterol derivatives have been shown to have a cytocidal effect on cervical cancer cells (Phytochemistr 7) 27, 2777
~2789 (1988). The same thing is true in Japanese Patent Publication No. 48-6766 and Japanese Patent Application Publication No. 55-1989.
It has also been reported in JP-A No. 71702 and Japanese Patent Application Laid-Open No. 58-62118.
〈発明が解決しようとする課題〉
しかし、ヤマブシタケについては上記のような報告がな
い、ヤマブシタケに含まれる化合物及びその癌細胞に対
する殺細胞効果については全く報告がないのである。<Problems to be Solved by the Invention> However, there are no reports as mentioned above regarding Yamabushitake, and there are no reports at all regarding the compounds contained in Yamabushitake and their cell-killing effects on cancer cells.
く課題を解決するための手段〉
しかして本発明者らは、以上の如き実情に鑑み、ヤマブ
シタケに含まれる化合物及びその癌細胞に対する殺細胞
効果について鋭意研究した結果、ヤマブシタケには特定
の化学構造から成る新規のフタリド誘導体が含まれてお
り、該フタリド誘導体は子宮頚癌細胞に対して優れた殺
細胞効果を有していることを見出した。Means for Solving the Problem> However, in view of the above-mentioned circumstances, the present inventors conducted extensive research on the compounds contained in Yamabushitake and their cytocidal effects on cancer cells, and found that Yamabushitake has a specific chemical structure. It has been found that this phthalide derivative has an excellent cell-killing effect on cervical cancer cells.
すなわち本発明は、下記構造式で示されるフタリド誘導
体、及び該フタリド誘導体を有効成分とする子宮頚癌細
胞の殺細胞剤に係わる。That is, the present invention relates to a phthalide derivative represented by the following structural formula, and a cell-killing agent for cervical cancer cells containing the phthalide derivative as an active ingredient.
上記構造式で示されるフタリド誘導体はヤマブシタケの
子実体を次のように処理することによって得られる。先
ず、ヤマブシタケの生成いは乾燥子叉体を水及び有機溶
媒の均一系で抽出処理し、濾過や遠心分離等で固液分離
したその抽出液から有機溶媒を蒸発して水相を得る。こ
の場合、水及び有機溶媒の均一系としては、８０〜８５
％メタノールやエタノール、８５％アセトン等がある。The phthalide derivative represented by the above structural formula can be obtained by treating the fruiting body of Yamabushitake mushroom as follows. First, produced or dried atomids of Yamabushitake are extracted with a homogeneous system of water and an organic solvent, and the organic solvent is evaporated from the extract, which is separated into solid and liquid by filtration, centrifugation, etc., to obtain an aqueous phase. In this case, as a homogeneous system of water and organic solvent, 80 to 85
% methanol, ethanol, 85% acetone, etc.
抽出は通常室温で行なうが、加熱還流してもよく、抽出
時間は通常１〜７２時間である０例えば。Extraction is usually carried out at room temperature, but may also be heated under reflux, and the extraction time is usually 1 to 72 hours.
８５％エタノール中にヤマブシタケの生子実体を加え、
ホモジナイズ処理し、これを室温で一昼夜放置した後、
濾過して抽出液を得、該抽出液を減圧下に４０〜４５℃
で加熱してエタノールを蒸発することにより水相を得る
のである０次に、該水相を水及び有機溶媒の混合系で液
液分配抽出処理して有機溶媒層を分取し１＃有機溶媒層
から有機溶媒を蒸発して乾固物を得る。この場合、有機
溶媒としては、クロロホルム、酢酸エチル、ジエチルエ
ーテル等があるが、収率の点でクロロホルムが好ましい
０例えば、上記水相にクロロホルムを加え、＃ｉ盪後、
放置して分層したクロロホルム層を分取し、該クロロホ
ルム層を減圧下に４０〜４５℃で加熱してクロロホルム
を蒸発することにより乾固物を得るのである。Add live fruiting bodies of Yamabushitake to 85% ethanol,
After homogenizing and leaving it at room temperature for a day and night,
Filter to obtain an extract, and heat the extract at 40-45°C under reduced pressure.
An aqueous phase is obtained by heating to evaporate the ethanol.Next, the aqueous phase is subjected to liquid-liquid distribution extraction using a mixed system of water and an organic solvent, and the organic solvent layer is fractionated. Evaporate the organic solvent from the layer to obtain a dry solid. In this case, examples of the organic solvent include chloroform, ethyl acetate, diethyl ether, etc., but chloroform is preferable from the viewpoint of yield. For example, chloroform is added to the above aqueous phase, and after
The chloroform layer separated by standing is separated, and the chloroform layer is heated at 40 to 45° C. under reduced pressure to evaporate the chloroform to obtain a dry product.
上記乾固物はそれ自体が子宮癌細胞の殺細胞剤として有
効なものであるが、該乾固物から不純物を除去してその
子宮頚癌細胞に対する殺細胞効果を高めるために、該乾
固物をクロマト分画処理するのが好ましく、クロマト分
画処理したものを更に再結晶処理するのがより好ましい
、この場合、詳しくは実施例で後述するように、ヘキサ
ン、クロロホルム、クロロホルム／アセトン等を展開溶
媒とするシリカゲルクロマトグラフィー或いは薄層クロ
マトグラフィーを用いてクロマト分画処理することがで
き、またクロロホルム／ジエチルエーテルを用いて再結
晶処理することができる。The dried product itself is effective as a cytocidal agent for uterine cancer cells, but in order to remove impurities from the dried product and enhance its cytocidal effect on cervical cancer cells, It is preferable to subject the substance to chromatographic fractionation, and it is more preferable to further recrystallize the chromatographed substance. In this case, as will be described in detail later in Examples, hexane, chloroform, chloroform/acetone, etc. Chromatographic fractionation can be performed using silica gel chromatography or thin layer chromatography as a developing solvent, and recrystallization can be performed using chloroform/diethyl ether.
かくして再結晶処理することにより単離される化合物の
物理化学的性質及び構造解析結果は下記の通りである。The physicochemical properties and structural analysis results of the compound isolated by the recrystallization treatment are as follows.
（１）分子量：３３０
（２）赤外線吸収スペクトル： ３３００−２８００．
１７６０．１８６０ｃｍ−１
（３）核磁気共鳴スペクトル（ｌ）ｆ−ＮＭＲ）： ｔ
、８１（ｓ）。(1) Molecular weight: 330 (2) Infrared absorption spectrum: 3300-2800.
1760.1860 cm-1 (3) Nuclear magnetic resonance spectrum (l) f-NMR): t
, 81(s).
１．９１（ｓ）、 ２．１７（ｓ）、 ３．１８（
ｓ）。1.91(s), 2.17(s), 3.18(
s).
３．５９（ｄ、８．４１）、３．８９（ｓ）、５．２５
（ｓ）。3.59 (d, 8.41), 3.89 (s), 5.25
(s).
５．３０（ｔ、 １３．４１）、 ８．０９（ｓ）
、 Ｅｌ、！３７（ｓ）（４）溶媒に対する溶解性：
酢酸エチル、クロロホルム、アセトンに可溶、ヘキサン
、メタノール、エタノールにやや可溶、水に不溶
（５）呈色反応：フォーリン反応陽性
（６）塩基性、中性、酸性の区別：酸性物質（７）色及
び形状：
白色結晶（融点１００〜１０２℃）
上記の物理化学的性質及び構造解析結果から、単離され
る化合物は前記構造式で示されるフタリド誘導体であり
、６−［（２°Ｅ）−３°、７”ジメチル−５゛〜オキ
ソ〜２′、６゛−オクタジェニル］−７−ヒドロキシ−
５−メトキシフタリドであることが決定された。5.30 (t, 13.41), 8.09 (s)
, El,! 37(s)(4) Solubility in solvents:
Soluble in ethyl acetate, chloroform, acetone, slightly soluble in hexane, methanol, ethanol, insoluble in water (5) Color reaction: Folin reaction positive (6) Basic, neutral, acidic distinction: Acidic substances (7) ) Color and shape: White crystals (melting point 100-102°C) From the above physicochemical properties and structural analysis results, the isolated compound is a phthalide derivative represented by the above structural formula, and 6-[(2°E) -3°,7''dimethyl-5'-oxo-2',6'-octagenyl]-7-hydroxy-
It was determined to be 5-methoxyphthalide.
〈実施例〉
・フタリド誘導体の抽出及び単敲
８５％エタノール６文にヤマブシタケの朱子実体７．３
ｋｇを加え、ホモジナイズ処理し、これを室温で一昼夜
放置した後、鑓過して抽出液を得た。残渣に８５％エタ
ノール４見を加え、同・様に抽出処理を行なって抽出液
を得、これを１回目の抽出液と合わせた。そして合わせ
た抽出液を減圧下に４０〜４５℃で加熱してエタノール
を蒸発することにより水相を得た。該水相にクロロホル
ム１文を加え、振盪後、放置して分層したクロロホルム
層を分取した。残渣にクロロホルム１９．を加え、同様
に液液分配抽出処理を行なってクロロホルム層を分取し
、１回目のクロロホルム層と合わせた。合わせたクロロ
ホルム層を減圧下に４０〜４５℃で加熱してクロロホル
ムを蒸発し、更にデシケータで乾燥して、乾固物（Ａ）
４．９９ｇを得た。<Example> - Extraction of phthalide derivatives and 6 volumes of 85% ethanol with 7.3 grams of vermilion fruiting body of Yamabushitake mushroom
kg was added, homogenized, and left at room temperature overnight, and then filtered to obtain an extract. Four portions of 85% ethanol were added to the residue, and extraction was performed in the same manner to obtain an extract, which was combined with the first extract. Then, the combined extracts were heated at 40 to 45° C. under reduced pressure to evaporate the ethanol, thereby obtaining an aqueous phase. One portion of chloroform was added to the aqueous phase, and after shaking, the mixture was left to stand and the separated chloroform layer was separated. Chloroform to the residue19. was added, and a liquid-liquid distribution extraction process was performed in the same manner to separate the chloroform layer, which was combined with the first chloroform layer. The combined chloroform layers were heated at 40 to 45°C under reduced pressure to evaporate the chloroform, and then dried in a desiccator to obtain a dry solid (A).
4.99g was obtained.
上記乾固物をヘキサンで溶解し、ワコーゲルＣ−２００
（和光紬薬社製）を用いてカラムクロマトグラフィーを
行なった。この際、展開溶媒として、順次極性が大きく
なるように、ヘキサン呻りロロホルム→クロロホルム／
アセトン（８／２）を各８０ｍ１用い、１０１の画分を
合計１８画分得た。このうちの第６及び７画分にについ
てクロロホルム／ジエチルエーテル（７／３）で再結晶
処理を行ない、この際の結晶析出の時間的ズレにより合
計３グループを得、このうちの第３グループから前記構
造式で示されるフタリド誘導体（Ｂ）３．０ｍｇを単離
した。Dissolve the above dry matter in hexane and add Wakogel C-200.
Column chromatography was performed using (manufactured by Wako Tsumugi Pharmaceutical Co., Ltd.). At this time, as a developing solvent, use hexane, loloform, chloroform, and
A total of 18 fractions (101 fractions) were obtained using 80 ml each of acetone (8/2). Of these, the 6th and 7th fractions were recrystallized with chloroform/diethyl ether (7/3), and due to the time lag in crystal precipitation, a total of 3 groups were obtained. 3.0 mg of the phthalide derivative (B) represented by the above structural formula was isolated.
一評価
継代培養した子宮頚癌細胞を、細胞数が４×１０’／＋
ｓｌとなるように、牛胎児血清１０％を含むイーグルＭ
ＥＭ培地で稀釈して、懸濁液を調製し、該懸濁液をプラ
スチック製９６穴マイクロプレート（コーニング社製）
の各式にそれぞれ２００ＩＬ１注入した。これを５％炭
酸ガス培養器中で３７°Ｃ１２４時間培養後、この培養
液中に薬剤溶液をそれぞれ５ＩＬ＋加え、更に上記と同
様の条件下で７２時間培養した。そして培地上清を除い
た上で細胞をメタノールで固定化し、ギムザ染色後、細
胞増殖の状態を鏡検した。薬剤溶液は、前記乾固物（Ａ
）及び前記フタリド誘導体（Ｂ）をそれぞれ種々の濃度
となるようにメタノールに溶解して作製した。Cervical cancer cells that have been subcultured for one evaluation have a cell number of 4 x 10'/+
Eagle M containing 10% fetal bovine serum to be sl
Dilute with EM medium to prepare a suspension, and transfer the suspension to a plastic 96-well microplate (manufactured by Corning).
200 IL1 was injected into each formula. After culturing this in a 5% carbon dioxide incubator at 37° C. for 124 hours, 5 IL+ of each drug solution was added to the culture solution, and the cells were further cultured for 72 hours under the same conditions as above. After removing the medium supernatant, the cells were fixed with methanol, and after Giemsa staining, the state of cell proliferation was examined under a microscope. The drug solution consists of the dried product (A
) and the phthalide derivative (B) were dissolved in methanol to various concentrations.
上記の鏡検下で殺細胞効果を調べ、生細胞数が全く認め
られない培地中の薬剤の最小濃度を最終有効濃度とした
。最終有効濃度は、乾固物（Ａ）の場合に１２５ ｇｇ
／層！であり、またフタリド誘導体（Ｂ）の場合にｌ
００ ｐ、、ｇ ／ｍｌであった。The cell-killing effect was examined under the above-mentioned microscopic examination, and the minimum concentration of the drug in the medium at which no viable cells were observed was defined as the final effective concentration. The final effective concentration is 125 gg in the case of dry matter (A)
/layer! and in the case of phthalide derivative (B), l
00 p,,g/ml.
〈発明の効果〉
以上説明した通りであるから、本発明に係る新規のフタ
リド誘導体は子宮頚癌細胞に対して優れた殺細胞効果を
有するという効果がある。<Effects of the Invention> As explained above, the novel phthalide derivative according to the present invention has an effect of having an excellent cell-killing effect on cervical cancer cells.
Claims (1)
宮頚癌細胞の殺細胞剤。[Claims] 1. A phthalide derivative represented by the following structural formula. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ 2. A cell-killing agent for cervical cancer cells containing the phthalide derivative according to claim 1 as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1295449A JP2792010B2 (en) | 1989-11-14 | 1989-11-14 | Phthalide derivative and cell killer for cervical cancer cells containing the same as active ingredient |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1295449A JP2792010B2 (en) | 1989-11-14 | 1989-11-14 | Phthalide derivative and cell killer for cervical cancer cells containing the same as active ingredient |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH03157379A true JPH03157379A (en) | 1991-07-05 |
| JP2792010B2 JP2792010B2 (en) | 1998-08-27 |
Family
ID=17820736
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1295449A Expired - Fee Related JP2792010B2 (en) | 1989-11-14 | 1989-11-14 | Phthalide derivative and cell killer for cervical cancer cells containing the same as active ingredient |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2792010B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007036074A1 (en) * | 2005-09-30 | 2007-04-05 | Fei Chen | The use of phthalide derivatives |
| CN108440380A (en) * | 2018-03-27 | 2018-08-24 | 湖南新汇制药股份有限公司 | A kind of compound detached from hedgehog fungus mycelium |
| KR20190093825A (en) * | 2018-02-01 | 2019-08-12 | 씨엔지유기농 영농조합법인 | Quantitative Analysis and Extraction Method of Indicator Components of Roebuck Mushroom |
-
1989
- 1989-11-14 JP JP1295449A patent/JP2792010B2/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007036074A1 (en) * | 2005-09-30 | 2007-04-05 | Fei Chen | The use of phthalide derivatives |
| JP2009511436A (en) * | 2005-09-30 | 2009-03-19 | チェン、フェイ | Use of phthalide derivatives |
| CN101272779B (en) | 2005-09-30 | 2012-09-05 | 陈菲 | Usage of phthalide derivant |
| US8445532B2 (en) | 2005-09-30 | 2013-05-21 | Fei Chen | Use of phthalide derivatives |
| KR20190093825A (en) * | 2018-02-01 | 2019-08-12 | 씨엔지유기농 영농조합법인 | Quantitative Analysis and Extraction Method of Indicator Components of Roebuck Mushroom |
| CN108440380A (en) * | 2018-03-27 | 2018-08-24 | 湖南新汇制药股份有限公司 | A kind of compound detached from hedgehog fungus mycelium |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2792010B2 (en) | 1998-08-27 |
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