JPH02247120A - Proliferation inhibitor against malignant tumor cells - Google Patents
Proliferation inhibitor against malignant tumor cellsInfo
- Publication number
- JPH02247120A JPH02247120A JP6392689A JP6392689A JPH02247120A JP H02247120 A JPH02247120 A JP H02247120A JP 6392689 A JP6392689 A JP 6392689A JP 6392689 A JP6392689 A JP 6392689A JP H02247120 A JPH02247120 A JP H02247120A
- Authority
- JP
- Japan
- Prior art keywords
- fraction
- medium
- malignant tumor
- heptadecanol
- culture
- 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.)
- Pending
Links
- 201000011510 cancer Diseases 0.000 title claims abstract description 13
- 210000004881 tumor cell Anatomy 0.000 title claims abstract description 13
- 239000003112 inhibitor Substances 0.000 title claims abstract description 9
- 230000035755 proliferation Effects 0.000 title description 2
- ZNYQHFLBAPNPRC-UHFFFAOYSA-N heptadecan-2-ol Chemical compound CCCCCCCCCCCCCCCC(C)O ZNYQHFLBAPNPRC-UHFFFAOYSA-N 0.000 claims abstract description 9
- 230000004663 cell proliferation Effects 0.000 claims description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 12
- 239000000203 mixture Substances 0.000 abstract description 9
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 abstract description 8
- 239000002609 medium Substances 0.000 abstract description 7
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 abstract description 6
- 210000004027 cell Anatomy 0.000 abstract description 6
- 238000010898 silica gel chromatography Methods 0.000 abstract description 6
- 239000001963 growth medium Substances 0.000 abstract description 5
- 235000012000 cholesterol Nutrition 0.000 abstract description 4
- 239000002904 solvent Substances 0.000 abstract description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 abstract description 3
- 239000013543 active substance Substances 0.000 abstract description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 abstract description 3
- 238000000605 extraction Methods 0.000 abstract description 3
- 239000000843 powder Substances 0.000 abstract description 3
- 210000002966 serum Anatomy 0.000 abstract description 3
- 241001465754 Metazoa Species 0.000 abstract description 2
- 208000002495 Uterine Neoplasms Diseases 0.000 abstract description 2
- 239000008213 purified water Substances 0.000 abstract description 2
- 230000002829 reductive effect Effects 0.000 abstract description 2
- 206010046766 uterine cancer Diseases 0.000 abstract description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 2
- 241000283690 Bos taurus Species 0.000 abstract 1
- 239000004480 active ingredient Substances 0.000 abstract 1
- 230000001605 fetal effect Effects 0.000 abstract 1
- 239000000706 filtrate Substances 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- 239000012679 serum free medium Substances 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 8
- 238000010586 diagram Methods 0.000 description 7
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 238000004949 mass spectrometry Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 5
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- 229930195729 fatty acid Natural products 0.000 description 4
- 239000000194 fatty acid Substances 0.000 description 4
- 150000004665 fatty acids Chemical class 0.000 description 4
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- GOQYKNQRPGWPLP-UHFFFAOYSA-N heptadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 1
- MDHYEMXUFSJLGV-UHFFFAOYSA-N beta-phenethyl acetate Natural products CC(=O)OCCC1=CC=CC=C1 MDHYEMXUFSJLGV-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 108700039708 galantide Proteins 0.000 description 1
- 230000009422 growth inhibiting effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- REIUXOLGHVXAEO-UHFFFAOYSA-N n-pentadecyl alcohol Natural products CCCCCCCCCCCCCCCO REIUXOLGHVXAEO-UHFFFAOYSA-N 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000002195 soluble material Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000007447 staining method Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003760 tallow Substances 0.000 description 1
- -1 trimethylsilyl (TMS) Chemical class 0.000 description 1
Abstract
Description
【発明の詳細な説明】
産業上の利用分野
本発明は、悪性腫瘍細胞増殖抑制剤に関するものである
。DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a malignant tumor cell proliferation inhibitor.
従来の技術
動物の悪性腫瘍細胞の培養後培地より前記悪性腫瘍細胞
を除き、残った培地をｎ−ブタノールを溶媒として抽出
操作を行い、次にこれを蒸発乾固したものからなる人の
悪性腫瘍細胞増殖抑制剤が特開昭６０−２８９３０号と
して提案されている。Prior Art After culturing animal malignant tumor cells, the malignant tumor cells are removed from the medium, the remaining medium is extracted using n-butanol as a solvent, and this is then evaporated to dryness. A cell proliferation inhibitor has been proposed in JP-A No. 60-28930.
発明が解決しようとする課題
しかし、前記従来の技術によって得られた悪性腫瘍細胞
増殖抑制剤は、有効物質が特定されていないため有機的
に合成することができず、製造コストが高いうえ不純物
が含まれているため増殖抑制効果が十分でなかった。Problems to be Solved by the Invention However, the malignant tumor cell proliferation inhibitors obtained by the above-mentioned conventional techniques cannot be organically synthesized because the effective substance has not been identified, and the manufacturing cost is high and impurities are present. However, the anti-proliferation effect was not sufficient.
本発明は、純粋で抑制効果が高く、安価な悪性腫瘍細胞
増殖抑制剤を提供することを目的とする。An object of the present invention is to provide a pure, highly suppressive, and inexpensive malignant tumor cell proliferation inhibitor.
課題を解決するための手段
本発明の人の悪性腫瘍細胞増殖抑制剤は、２ヘプタデカ
ノールからなることを特徴どするものであのる。Means for Solving the Problems The human malignant tumor cell proliferation inhibitor of the present invention is characterized by comprising 2-heptadecanol.
発明の効果
本発明の悪性腫瘍細胞増殖抑制剤は、２−ヘプタデカノ
ールが有機合成可能であるため安価な抗腫瘍剤として供
給でき、悪性ｆｆ１ｌｉ瘍細胞増殖抑制効果も高い。Effects of the Invention The malignant tumor cell proliferation inhibitor of the present invention can be supplied as an inexpensive antitumor agent because 2-heptadecanol can be organically synthesized, and has a high effect of suppressing the proliferation of malignant ff1li tumor cells.
また、正常細胞に対しても多少の増殖抑制作用は認めら
れるが、悪性腫瘍細胞に対する増殖抑制力とは著しい差
異があり、在来の抗腫瘍剤のような副作用はほとんどな
い。In addition, although some growth-inhibiting effects are observed on normal cells, there is a marked difference in the ability to suppress the growth of malignant tumor cells, and there are almost no side effects like conventional anti-tumor agents.
実施例 以下、実施例により説明する。Example Examples will be explained below.
１〉製 法
１０％牛新生児血清を添加したイーグルのＭＥＭ培地（
細菌学実習提要、東大医科学研究所学友会編、４１２頁
参照）を生長用培地及び抽出用の培地として使用する。1> Production method Eagle's MEM medium supplemented with 10% neonatal bovine serum (
Bacteriology Practice Handbook, edited by the University of Tokyo Institute of Medical Science Alumni Association, p. 412) is used as the growth medium and extraction medium.
まず、人子宮癌由来のＨｅ１ａ細胞（Ｓ３）を成長用培
地で５日間３７℃で前培養し、その後１回洗って血清を
除く。次に、これを抽出用培地に３１中に移植し、５％
炭酸ガス畔卵器中３５℃で静置培養する。このとき１０
日間ぐらいまで培養を続ける。First, human uterine cancer-derived He1a cells (S3) are precultured in a growth medium at 37° C. for 5 days, and then washed once to remove serum. Next, this was transplanted into an extraction medium of 31% and 5%
Static culture is carried out at 35°C in a carbon dioxide tank. At this time 10
Continue culturing for about a day.
この培養物を凍結乾燥して３１の培地から約４５（］の
吸湿性粗粉末を得、このうち１００を５００１１１ｊ！
のメタノールに懸濁し、よく撹拌してメタノール可溶物
を分離し、溶媒を減圧留去する。This culture was freeze-dried to obtain approximately 45 (] of hygroscopic crude powder from 31 media, of which 100 was 500111j!).
The mixture was suspended in methanol, stirred thoroughly to separate methanol-soluble materials, and the solvent was distilled off under reduced pressure.
これを２００ｍ１の精製水中で溶解し、稀アンモニア水
にてＰＨ８，０とした後、周間のブタノールで３回抽出
する。This was dissolved in 200 ml of purified water, adjusted to pH 8.0 with dilute aqueous ammonia, and then extracted three times with butanol.
この操作を繰返して、８１４ｎ＋ｏの粗酒性物質（Ｈｅ
ｌａ−８Ｂと称する〉を得る。By repeating this operation, 814n+o crude alcoholic substance (He
(referred to as la-8B) was obtained.
このようにして得た活性物質＠ ｅｌａ−８Ｂをシリカ
ゲル充填のカラム（直径４ ｃｍ、長さ３０ｃｍ）に通
し、クロロホルム、メタノール、１７１％アンモニア水
（容積比１００：３０：１．２＞の混合液により溶出し
、活性分画を集めた。The active substance @ ela-8B thus obtained was passed through a column packed with silica gel (diameter 4 cm, length 30 cm) and mixed with chloroform, methanol, and 171% aqueous ammonia (volume ratio 100:30:1.2). The active fractions were collected.
さらに、その活性分画をシリカゲル・カラムクロマトグ
ラフ（直径３ ｃｍ、長さ５Ｑｃｍ）でヘキザン、酢酸
エステル（７：１）で溶出し、さらにその比を５＝１に
かえて溶出し、活性物質１５Ｉ（Ｉｔを得た。この活性
のある４つのフラクションを極性の低い順に記すと次の
とおりである。Further, the active fraction was eluted with hexane and acetate (7:1) using a silica gel column chromatograph (diameter 3 cm, length 5 Q cm), and then the ratio was changed to 5=1 to elute the active substance. 15I (It) was obtained. The four active fractions are listed in descending order of polarity as follows.
（１）長鎖アルカノールフラクション
コレステロールよりやや極性の低い活性のあるフラクシ
ョンを集め、再度シリカゲルカラムクロマトグラフィで
精製する。(1) Long-chain alkanol fraction The active fraction, which is slightly less polar than cholesterol, is collected and purified again by silica gel column chromatography.
溶出にはｎ−ヘキサンと酢酸エチルを
５：１で混合した溶出液を用い、活性物質（Ｈｅｌａ−
８８＞９．８０より４０ｍｇのフラクションを得た。The active substance (Hela-
Since 88>9.80, a 40 mg fraction was obtained.
この一部をそのまま及びトリメチルシリル（ＴＭＳ＞ａ
導体としてガスクロマトグラフ質量分析（ＧＣ−ＭＳ）
にて分析し、本フラクションは２−ヘプタデカノールを
主成分とする混合物からなることがわかった。Part of this was used as is and trimethylsilyl (TMS>a
Gas chromatography mass spectrometry (GC-MS) as a conductor
It was found that this fraction consisted of a mixture containing 2-heptadecanol as the main component.
そのまま分析した結果を第１図に、ＴＭＳ体として分析
した結果を第２図に示し、さらに、磁気共鳴（ＮＭＲ）
のデータを第５図に小す。Figure 1 shows the results of the analysis as it is, Figure 2 shows the results of the analysis as a TMS body, and furthermore, the results of the analysis using magnetic resonance (NMR) are shown in Figure 1.
The data are shown in Figure 5.
また、質量分析（ＭＳ）のデータ及びＮＭＲのデータよ
り決定された成分の構造を表１にボす。Table 1 also shows the structures of the components determined from mass spectrometry (MS) data and NMR data.
表１
さらに、本フラクションのＮＭＲ（重水素化クロロホル
ムの化学シフト値は第５図に示すとおり）であり、２−
ヘプタデカノールが主成分であることと合致する。Table 1 Furthermore, the NMR of this fraction (the chemical shift value of deuterated chloroform is shown in Figure 5) is 2-
This is consistent with heptadecanol being the main component.
なお、合成した２−ヘプタデカノールをそのままでＧＯ
−ＭＳにて分析した結果（第２図参照）、及びＴＭＳ体
として分析した結果（第４図参照）、ＧＣの保持時間及
びＭ’Ｓが本フラクションの主成分と完全に一致した。In addition, the synthesized 2-heptadecanol can be directly used as GO.
-The results of analysis by MS (see Figure 2) and the results of analysis as a TMS body (see Figure 4) showed that the GC retention time and M'S completely matched the main component of this fraction.
また、ＮＭＲも近似していた。Moreover, the NMR values were also similar.
（２）フェノール性成分
コレステロールよりやや極性の低い、塩化鉄（ＩＩＩ）
で褐色に焼ける紫外吸収のある、活性のあるフラクショ
ンを集め、ヘキザン、酢酸エチル（容積比４：１〜３：
１）の混合液を溶出液とし、再度シリカゲルカラムクロ
マトグラフィで精製し、Ｈｅ１ａ−８Ｂ ９．８ｇよ
り３９ＩＩ１ｇの油状物質を得た。(2) Iron (III) chloride, which is slightly less polar than phenolic component cholesterol
Collect the active fraction with ultraviolet absorption that burns brown and add hexane and ethyl acetate (volume ratio 4:1 to 3:
The mixture of 1) was used as an eluent and purified again by silica gel column chromatography to obtain 1 g of 39II oily substance from 9.8 g of He1a-8B.
この油状物質の１３０の核磁気共鳴吸収（第６図参照）
の結果、及びこの油状物質をそのままでＭＳにて分析（
第７図参照）ざらにＴＭＳ誘導体としてＭＳにて分析（
第８図参照）した結果、２−ヒドロキシ−１−（Ｐ−ヒ
ドロキシフェニール）−５−メチルヘキサン３−ワンが
見出された。130 nuclear magnetic resonance absorption of this oily substance (see Figure 6)
As a result, this oily substance was analyzed as it is by MS (
(See Figure 7) Analyzed by MS as a TMS derivative (
(see Figure 8), 2-hydroxy-1-(P-hydroxyphenyl)-5-methylhexane 3-one was found.
その構造式は次のとおりであることがわかる。It can be seen that its structural formula is as follows.
または、
（３）脂肪酸フラクション
シリカゲルカラムクロマトグラフィで集めた脂肪酸フラ
クションを、ベンゼン、酢酸エチル（容積比２：１〜１
：１、但し１％の酢酸を含む）の混液を用い、再度シリ
カゲルカラムクロマトグラフィで精製し、Ｈｅ１ａ−８
Ｂ３．１ｇより１２５ｍ（ｌの本フラクションを得た。(3) Fatty acid fraction The fatty acid fraction collected by silica gel column chromatography is mixed with benzene and ethyl acetate (volume ratio 2:1 to 1).
:1, but containing 1% acetic acid), was purified again by silica gel column chromatography, and He1a-8
125 m (l) of this fraction was obtained from 3.1 g of B.
本フラクションの一部をジアゾメタンにてメチルエステ
ル誘導体としてＧ Ｃ−Ｍ Ｓにて分析した結果、第９
図に示すように本フラクションはいくつかの脂肪酸混合
物であることがわかった。As a result of analyzing a part of this fraction with diazomethane as a methyl ester derivative by G C-MS, it was found that
As shown in the figure, this fraction was found to be a mixture of several fatty acids.
ＧＣ−ＭＳのデータより決定された成分を表２に示す。Table 2 shows the components determined from the GC-MS data.
表２
（４）モノグリセライドフラクション
シリカゲルカラムクロマトグラフィでコレステロールよ
り遥かに極性の高い活性のあるフラクションを集め、こ
れをベンゼン、酢酸エチル（容積比１：１〜１：２）の
混液を溶出液とし再度シリカゲルカラムクロマトグラフ
ィで精製し、Ｈｅ１ａ−８Ｂ ９．８ｇより１．５＋
ｎｇの本フラクションを得た。Table 2 (4) Monoglyceride fraction Collect the active fraction, which is much more polar than cholesterol, by silica gel column chromatography and reuse it on silica gel using a mixture of benzene and ethyl acetate (volume ratio 1:1 to 1:2) as the eluent. Purified by column chromatography, 1.5+ from 9.8g of He1a-8B
ng of this fraction were obtained.
本フラクションはＮＭＲにてグリセライド様スペクトル
を示しく第１２図参照）、薄層クロマトグラフ（ＴＬＣ
）でＲｆ値は０．１（展開溶媒ベンゼン−酢酸エチル２
：１）であり、ｉ −ｍｏｎｏｌｉｎｏｌｅｎｏｙｌ
ｇｌｙｃｅｒｏｌ と一致した。This fraction shows a glyceride-like spectrum in NMR (see Figure 12) and thin layer chromatography (TLC).
) and the Rf value is 0.1 (developing solvent benzene-ethyl acetate 2
:1) and i-monolinolenoyl
It was consistent with glycerol.
また、アセチル化により２個のアセテートが入ることか
らもモノグリセライドであると考えられ、本フラクショ
ンの一部をトリメチルシリル（ＴＭＳ）誘導体としてＧ
Ｏ−Ｍ Ｓにて分析した結果、第１０図及び第１１図
に小すように、本フラクションは主成分をペンタデカノ
ールグリセライドとするいくつかの混合物からなること
がわかった。In addition, it is thought that it is a monoglyceride because two acetates are introduced by acetylation, and a part of this fraction is converted into a trimethylsilyl (TMS) derivative.
As a result of analysis by O-MS, it was found that this fraction was composed of several mixtures whose main component was pentadecanol glyceride, as shown in FIGS. 10 and 11.
ＧＣ−ＭＳのデータより決定された成分を表３に示す。Table 3 shows the components determined from the GC-MS data.
表３
なお、これらが、２−モノグリセライドではなく、１−
モノグリセライドであることは、マススペクトルの解裂
パターンにおいてＭ−１５゜Ｍ−ＴＭＳＯＣＨ２が強く
でること（Ｌｉｐｉｄｉｓｌ、３７１（１９６６））よ
り明らかである。Table 3 Note that these are not 2-monoglycerides, but 1-monoglycerides.
The fact that it is a monoglyceride is clear from the strong appearance of M-15°M-TMSOCH2 in the dissociation pattern of the mass spectrum (Lipidisl, 371 (1966)).
２）抗腫瘍活性の検定
次に、２−ヘプタデカノールを主成分とする長鎖アルカ
ノールフラクションの抗癌作用について検討する。悪性
腫瘍細胞試料としてＨｅｌａ−８３及び白面癌細胞Ｌ−
５１７８Ｙ、Ｌ−１２１０を１Ｘ１０”ケを１０％牛脂
児血清添加の出版合成培地ＲＰＭＩ−１６／ｉｏに移植
し、３７°Ｃで炭酸ガスインキュベータで４８Ｒ間培養
後、その生細胞を１〜リパンブル一染色法で決定して■
ｃ５゜（半数の細胞増殖を抑制する試Ｉｆ ｆＪ度μ（
］／ ｍｌ ）を求めた。なお、ｌ−１ｅ ｌ ａ細胞
の場合は３１目に判定した。2) Assay of antitumor activity Next, the anticancer effect of the long chain alkanol fraction containing 2-heptadecanol as a main component will be examined. Hela-83 and Shiramen cancer cell L- as malignant tumor cell samples
5178Y, L-1210 were transplanted into published synthetic medium RPMI-16/io containing 10% tallow serum and cultured for 48R in a carbon dioxide gas incubator at 37°C. Determined by staining method■
c5゜(Test to suppress half of cell proliferation If fJ degree μ(
]/ml) was determined. In addition, in the case of l-1e la cells, the determination was made at the 31st day.
その結果を表４に示づ５、 表４The results are shown in Table 45. Table 4
第１図は、長鎖アルカノールフラクションをそのままＧ
Ｃ−ＭＳにて分析した図、
第２図は、長鎖アルカノールフラクションをＴＭＳ誘導
体としてＧＯ−ＭＳにて分析した図、第３図は、合成２
−ヘプタデカノールをそのままＧＣ−ＭＳにて分析した
図、
第４図は、合成２−ヘプタデカノールをＴＭＳ誘導体と
してＧＣ−ＭＳにて分析した図、第５図は、長鎖アルカ
ノールフラクションのＮＭＲを示す図、
第６図は、同上の１３０−ＮＭＲを示す図、第７図は、
フェノール性成分をそのままでＭＳにて分析、した図、
第８図は、フェノール性成分をＴＭＳ誘導体としてＭＳ
にて分析した図、
第９図は、脂肪酸フラクションをメチルエステル誘導体
としてＧＣ−ＭＳにて分析した図、第１０図は、１−ｍ
ｏｎｏｌｉｎｏｌｅｎｏｙｌ ｇｌｙｃｅｒｏｌ ｄＴ
ＭＳエーテルのＧＣ−ＭＳ分析図、
第１１図は、モノグリセライドフラクションをＴＭＳ誘
導、体にて分析した図、
第１２図は、モノグリセライドフラクションのＮＭＲを
示す図である。
璧具菌趣旧Figure 1 shows the long-chain alkanol fraction as it is.
Figure 2 is a diagram of long-chain alkanol fraction analyzed by GO-MS as a TMS derivative, Figure 3 is a diagram of synthesis 2.
-Heptadecanol as it is analyzed by GC-MS. Figure 4 is a GC-MS analysis of synthesized 2-heptadecanol as a TMS derivative. Figure 5 is NMR of a long-chain alkanol fraction. Figure 6 is a diagram showing 130-NMR of the same as above, Figure 7 is a diagram showing 130-NMR of the same as above.
Figure 8 shows the phenolic components analyzed by MS as they are.
Figure 9 shows the analysis of the fatty acid fraction as a methyl ester derivative by GC-MS, and Figure 10 shows the analysis of the 1-m
onolinolenoyl glycerol dT
GC-MS analysis diagram of MS ether; Figure 11 is a diagram showing the monoglyceride fraction analyzed by TMS induction in the body; Figure 12 is a diagram showing the NMR of the monoglyceride fraction. Old-fashioned fungus
Claims (1)
性腫瘍細胞増殖抑制剤。A human malignant tumor cell proliferation inhibitor comprising 2-heptadecanol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6392689A JPH02247120A (en) | 1989-03-17 | 1989-03-17 | Proliferation inhibitor against malignant tumor cells |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6392689A JPH02247120A (en) | 1989-03-17 | 1989-03-17 | Proliferation inhibitor against malignant tumor cells |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH02247120A true JPH02247120A (en) | 1990-10-02 |
Family
ID=13243436
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6392689A Pending JPH02247120A (en) | 1989-03-17 | 1989-03-17 | Proliferation inhibitor against malignant tumor cells |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH02247120A (en) |
-
1989
- 1989-03-17 JP JP6392689A patent/JPH02247120A/en active Pending
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