JPH021498A - Polyene substance and agent for controlling mast cell function - Google Patents
Polyene substance and agent for controlling mast cell functionInfo
- Publication number
- JPH021498A JPH021498A JP1055862A JP5586289A JPH021498A JP H021498 A JPH021498 A JP H021498A JP 1055862 A JP1055862 A JP 1055862A JP 5586289 A JP5586289 A JP 5586289A JP H021498 A JPH021498 A JP H021498A
- Authority
- JP
- Japan
- Prior art keywords
- substance
- mast cell
- cell function
- polyene
- 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
- 239000000126 substance Substances 0.000 title claims abstract description 50
- 210000003630 histaminocyte Anatomy 0.000 title claims abstract description 23
- 230000003915 cell function Effects 0.000 title claims abstract description 9
- 150000004291 polyenes Chemical class 0.000 title claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 15
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims 2
- 125000000468 ketone group Chemical group 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 7
- 239000000463 material Substances 0.000 abstract description 6
- 150000001768 cations Chemical class 0.000 abstract description 5
- 241000933209 Streptomyces eurocidicus Species 0.000 abstract description 3
- 238000012258 culturing Methods 0.000 abstract description 2
- 150000002576 ketones Chemical class 0.000 abstract description 2
- 241000187220 Streptomyces albireticuli Species 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 28
- 210000004027 cell Anatomy 0.000 description 17
- 239000000243 solution Substances 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical group O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 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 description 8
- 238000000034 method Methods 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000003463 adsorbent Substances 0.000 description 5
- 229920002055 compound 48/80 Polymers 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- 229960001340 histamine Drugs 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 235000012000 cholesterol Nutrition 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 238000001179 sorption measurement Methods 0.000 description 4
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical class CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 229910001424 calcium ion Inorganic materials 0.000 description 3
- 229920001429 chelating resin Polymers 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 235000013372 meat Nutrition 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 239000001888 Peptone Substances 0.000 description 2
- 108010080698 Peptones Proteins 0.000 description 2
- 241000187747 Streptomyces Species 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- GPZPVAIBXPRLFD-UHFFFAOYSA-N acetic acid;azane Chemical compound N.N.CC(O)=O GPZPVAIBXPRLFD-UHFFFAOYSA-N 0.000 description 2
- ALSPKRWQCLSJLV-UHFFFAOYSA-N azanium;acetic acid;acetate Chemical compound [NH4+].CC(O)=O.CC([O-])=O ALSPKRWQCLSJLV-UHFFFAOYSA-N 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 229940041514 candida albicans extract Drugs 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 238000004255 ion exchange chromatography Methods 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 235000019319 peptone Nutrition 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000012138 yeast extract Substances 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- HIYAVKIYRIFSCZ-CVXKHCKVSA-N Calcimycin Chemical compound CC([C@H]1OC2([C@@H](C[C@H]1C)C)O[C@H]([C@H](CC2)C)CC=1OC2=CC=C(C(=C2N=1)C(O)=O)NC)C(=O)C1=CC=CN1 HIYAVKIYRIFSCZ-CVXKHCKVSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 108010062580 Concanavalin A Proteins 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000004847 absorption spectroscopy Methods 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 238000005377 adsorption chromatography Methods 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- HIYAVKIYRIFSCZ-UHFFFAOYSA-N calcium ionophore A23187 Natural products N=1C2=C(C(O)=O)C(NC)=CC=C2OC=1CC(C(CC1)C)OC1(C(CC1C)C)OC1C(C)C(=O)C1=CC=CN1 HIYAVKIYRIFSCZ-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- CDVMXMZPDJHSCC-UHFFFAOYSA-N chembl1684662 Chemical compound C=1C=C2C=C(C=3C4=NC=CC=C4NN=3)NC2=CC=1CC(=O)C1=CC=CC=C1 CDVMXMZPDJHSCC-UHFFFAOYSA-N 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 238000002350 laparotomy Methods 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000000401 methanolic extract Substances 0.000 description 1
- -1 methoxy, ethoxy Chemical group 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- DTSSDPFTHGBSDX-KVTDHHQDSA-N mycosamine Chemical compound C[C@@H](O)[C@@H](O)[C@H](N)[C@H](O)C=O DTSSDPFTHGBSDX-KVTDHHQDSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- YWAKXRMUMFPDSH-UHFFFAOYSA-N pentene Chemical group CCCC=C YWAKXRMUMFPDSH-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000002336 sorption--desorption measurement Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002495 two-dimensional nuclear magnetic resonance spectrum Methods 0.000 description 1
- 241001446247 uncultured actinomycete Species 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
【発明の詳細な説明】
〔技術分野〕
本発明は、ポリエン物質及び肥満細胞機能調節剤に関す
るものである。DETAILED DESCRIPTION OF THE INVENTION [Technical Field] The present invention relates to a polyene substance and a mast cell function regulator.
肥満細胞は動物の結合組織及び消化管粘膜内に存在し、
細胞内にケミカルメデイエータ−と呼ばれる生物活性物
質を含む顆粒を数多く持っている。Mast cells are present in the connective tissue and gastrointestinal mucosa of animals,
Inside the cell, there are many granules containing biologically active substances called chemical mediators.
炎症反応及びアレルギー反応はともに、刺激を受けた肥
満細胞が脱顆粒反応を起こし、ヒスタミン、セロ1−ニ
ンなどのケミカルメデイエータ−を放出するところから
始まる。免疫グロブリンEの受容体を持つ細胞として肥
満細胞が注目され、肥ill細胞における刺激の伝達機
構及び脱顆粒反応の作用機作などを解明することがアレ
ルギー反応を理解することに直接つながるため、肥満細
胞の脱顆粒作用及び脱顆粒抑制作用等の機能調節作用を
もつ物質の開発が望まれている。Both inflammatory and allergic reactions begin when stimulated mast cells undergo a degranulation reaction and release chemical mediators such as histamine and sero-1-nin. Mast cells are attracting attention as cells that have receptors for immunoglobulin E, and elucidation of the stimulus transmission mechanism and degranulation reaction mechanism in mast cells will directly lead to understanding allergic reactions. There is a desire to develop substances that have functional regulating effects such as cell degranulation and degranulation inhibiting effects.
そこで、本発明者らは、このような作用を有する物質の
開発について広く検討を行ったところ、下記一般式で示
される新規なポリエン物質が肥満細胞機能調節作用を有
することをはじめて明らかにし、本発明を完成させた。Therefore, the present inventors extensively investigated the development of a substance with such an effect, and found for the first time that a new polyene substance represented by the general formula below has a mast cell function regulating effect, and the present inventors Completed the invention.
従って、本発明は新規なポリエン物質及び肥満細ノ泡機
能調節剤を提供することを目的とする。Therefore, it is an object of the present invention to provide a novel polyene material and an obese cell function regulator.
本発明によれば、下記一般式で示されるポリエン物質及
び肥満細胞機能調節剤が提供される。According to the present invention, a polyene substance and a mast cell function regulator represented by the following general formula are provided.
前記式中、R1は水素原子又はアルキル基であり、アル
キル基としては、メチル、エチル、プロピル等の低級ア
ルキル基が挙げられる。R2は水素〃バ子、水lf!
J!、アルキル基、アルコキシ基又はケトンJ、(であ
り、アルキル基としては、メチル、エチル。In the above formula, R1 is a hydrogen atom or an alkyl group, and examples of the alkyl group include lower alkyl groups such as methyl, ethyl, and propyl. R2 is hydrogen, water lf!
J! , an alkyl group, an alkoxy group or a ketone J, (where the alkyl group is methyl, ethyl.
プロピル等の低級アルキル基、アルコキシ基としては、
メトキシ、エトキシ、プロポキシ等の低級アルコキシ基
が挙げられる。R2としては、特に水素原子又は水酸基
が好ましい。R3は水素原子、塩形成性カチオン又はア
ルキル基である。塩形成性カチオンとしては、ナトリウ
ムやカリウム等のアルカリ金属、カルシウムやマグネシ
ウム等のアルカリ土類金属の他、アルミニウム、アンモ
ニウム。As lower alkyl groups such as propyl, alkoxy groups,
Examples include lower alkoxy groups such as methoxy, ethoxy, and propoxy. R2 is particularly preferably a hydrogen atom or a hydroxyl group. R3 is a hydrogen atom, a salt-forming cation or an alkyl group. Examples of salt-forming cations include alkali metals such as sodium and potassium, alkaline earth metals such as calcium and magnesium, as well as aluminum and ammonium.
有機アンモニウム等が挙げられる。アルキル基としては
、メチル、エチル、プロピル等の低級アルキル基が挙げ
られる。Examples include organic ammonium. Examples of the alkyl group include lower alkyl groups such as methyl, ethyl, and propyl.
前記一般式(1)において、1(3が水素原子であるポ
リエン物質(以下、本物質とも言う)は、ストレプトベ
ルティシリウム・ユーロシジカム(Streptovc
rticillium eurocidicum、IF
ON(L13491)株又はストレプトベルティシリウ
ム・アルビレティキュリ(Streptovertic
illjum albireticuli、 IFON
(112737)株を、一般培地に培養し、培地中に産
生させることができる。この場合の培養は、例えば、炭
素源としてグルコース、シュークロース、マルl−−ス
、デキトリン、 lIU粉、グリセリン等を。In the general formula (1), the polyene substance (hereinafter also referred to as the present substance) in which 1 (3) is a hydrogen atom is Streptovcillium eurocidicum (Streptovcillium eurocidicum).
rticillium eurocidicum, IF
ON (L13491) strain or Streptoverticillium albireticulli (Streptoverticillium
illjum albireticuli, IFON
(112737) strain can be cultured and produced in a general medium. In this case, the culture uses, for example, glucose, sucrose, maltose, dextrin, lIU powder, glycerin, etc. as a carbon source.
窒素源としてはパブ1−ン、肉エキス、酵母エキス、麦
芽エキス等を用い、さらに無機塩として、NaCQ 、
K2H1)04、Na211PO,、MgSO4等を
加えた中性液体培地中で、通気、撹拌することにより実
施することができる。培地のpHは5〜8、好ましくは
7付近で培養される。培養温度は通常、20〜35℃の
範囲であるが、30℃付近が好ましい。例えばグルコー
ス1.5%、ペプトン0.5%、肉エキス0.5%、酵
母エキス0.5%、NaCQ O,5%を含むPH7,
0の液体培地で28℃、40時間培養することにより、
本物質を生産させることができる。As the nitrogen source, pub 1-, meat extract, yeast extract, malt extract, etc. are used, and as an inorganic salt, NaCQ,
This can be carried out by aeration and stirring in a neutral liquid medium to which K2H1)04, Na211PO, MgSO4, etc. are added. Culture is carried out at a pH of 5 to 8, preferably around 7. The culture temperature is usually in the range of 20 to 35°C, preferably around 30°C. For example, PH7 containing 1.5% glucose, 0.5% peptone, 0.5% meat extract, 0.5% yeast extract, 5% NaCQO,
By culturing in a liquid medium of 0 at 28°C for 40 hours,
This substance can be produced.
培養濾液からの本物質の採取は、有機溶媒抽出法、イオ
ン交換樹脂法、及び吸着剤を用いた吸脱着法や、高速液
体クロマトグラフィー法等を用いて行うことができる。The present substance can be collected from the culture filtrate using an organic solvent extraction method, an ion exchange resin method, an adsorption/desorption method using an adsorbent, a high performance liquid chromatography method, or the like.
例えば、培養濾液中に1/lO体積量のアンバーライト
XAD −7を加えて時々撹拌しながら室温で約4時間
服着処理を行った後、アンバーライトXAD −7を濾
別し、これを洗浄後、80%メタノール溶液で溶出処理
する。溶出液を減圧濃縮後、水に再溶解し、p 114
、0に調整した後、C阿−トヨパールイオン交換クロ
マトグラフィーを行うと、0.05M酢酸−酢酸アンモ
ニウムによるpHグラジェントによりpl+5.0付近
から溶出が始まる。For example, after adding 1/10 volume of Amberlite XAD-7 to the culture filtrate and performing a dressing treatment at room temperature for about 4 hours with occasional stirring, Amberlite XAD-7 is filtered and washed. Afterwards, elution treatment is performed with an 80% methanol solution. After concentrating the eluate under reduced pressure, it was redissolved in water, p 114
After adjusting the pH to 0, C-Toyopearl ion exchange chromatography is performed, and elution begins around pl+5.0 due to a pH gradient of 0.05M acetic acid-ammonium acetate.
この溶出液をさらにpH9,0に調整し、DEAE −
トヨパールイオン交換クロマトグラフィーを行うとPH
7,5付近から溶出が始まる。さらに活性画分を、NC
IゲルCHP−20P吸着カラムに吸着させ、40%ア
セトニトリル溶出画分を分取した後、高速液体クロマト
グラフィー(IIPLC)を用いることにより本物質を
得ることができる。This eluate was further adjusted to pH 9.0 and DEAE-
When Toyopearl ion exchange chromatography is performed, the pH
Elution begins around 7.5. Furthermore, the active fraction was
This substance can be obtained by adsorbing it on an I-gel CHP-20P adsorption column, collecting a 40% acetonitrile elution fraction, and then using high performance liquid chromatography (IIPLC).
さらに1本物質は菌体をメタノール等の有機溶媒を用い
る抽出処理した後、ODSカラム等による吸着クロマト
グラフィーを用い、溶出画分を濃縮、結晶化等の通常の
精製操作を行うことによっても得ることができる。Furthermore, this substance can also be obtained by extracting the bacterial cells using an organic solvent such as methanol, then using adsorption chromatography using an ODS column, etc., and performing normal purification operations such as concentration and crystallization of the eluted fraction. be able to.
前記、一般式(1)において1<3が塩形成性カチオン
及びアルキル基を示すものは、一般式(1)においてR
3が水素原子を示す物質に対し、それぞれ対応するカチ
オンを含む塩基及びエステル化剤を常法により反応させ
ることによって得ることができる。In the above general formula (1), 1<3 represents a salt-forming cation and an alkyl group, R
It can be obtained by reacting a substance in which 3 represents a hydrogen atom with a base containing a corresponding cation and an esterifying agent in a conventional manner.
また、本物質は1通常用いらる化学合成法もしくはe索
を用いる合成法によっても得ることができる。ポリエン
物質あるいはそれに類するものとマイコースもしくはマ
イコサミンなどを用いることにより本物質を合成するこ
とができる。Further, the present substance can also be obtained by a commonly used chemical synthesis method or a synthesis method using an e-cord. This substance can be synthesized by using a polyene substance or a similar substance and mycose or mycosamine.
次に、本発明を実施例によりさらに詳細に説明する。 Next, the present invention will be explained in more detail with reference to Examples.
実施例1
グルコース1.5%、ペプトン0.5%、肉エキス0.
5%、t!/p母エキス0.5%、NaCQ O,5%
を含むpH7,0の液体培地100m12を500m
Qの坂ロフラスコに分注し、120℃、20分間滅菌す
る。この培地に放線菌ストレプトベルティシリウム・ユ
ーロシジカム株の斜面寒天培地より1白金耳歇を接種し
、28℃、3日間往復しんどう培養を行った。この培養
液と同組成の培地20Qを30Q用ジャーファーメンタ
−に仕込み、ストレプトベルティシリウム・ユーロシジ
カム株の前培養液300m Qをこの培地に移し、28
℃、200回転1通気量毎分lOQで40時間培養を行
った。培養終了後、7000回転の連続遠心を行うこと
により、菌体と培養濾液とを分離し、黒かっ色の培養濾
液18gを得た。この培養濾液の肥満細胞脱顆粒抑制活
性は642,500ユニツトであった。Example 1 Glucose 1.5%, peptone 0.5%, meat extract 0.
5%, t! /p mother extract 0.5%, NaCQ O, 5%
500 m of 100 m of liquid medium containing pH 7.0
Dispense into a Q Sakalo flask and sterilize at 120°C for 20 minutes. One platinum loop from a slanted agar medium of the actinomycete Streptoverticillium eurocidicum strain was inoculated into this medium, and cultured in a reciprocating manner at 28°C for 3 days. A medium 20Q with the same composition as this culture solution was placed in a jar fermenter for 30Q, and 300 mQ of a preculture solution of Streptoverticillium eurocidicum strain was transferred to this medium.
Culture was carried out for 40 hours at 200° C. and 1 air flow per minute. After the culture was completed, the bacterial cells and the culture filtrate were separated by continuous centrifugation at 7000 rpm to obtain 18 g of a dark brown culture filtrate. The mast cell degranulation inhibitory activity of this culture filtrate was 642,500 units.
実施例2
実施例1で得た菌体に5倍量のメタノールを加えて撹拌
後、室温にて放置した。時々撹拌しながら24時間装い
た後、菌体を濾別後、メタノール抽出液を同容量の水と
混合して、ODS吸着カラム(日本ミリポア製、カラム
体積778成、メタノール/水=171にて平衡化)に
吸着させた。溶出液(メタノール/水=2/1)を用い
て1、■及びlitの両分を順次得、濃縮、再結晶操作
により、各両分に対応する本物質Nal:5.0mg、
Na2:8.7mH及びNa3:loOmgを得た。Example 2 Five times the amount of methanol was added to the bacterial cells obtained in Example 1, stirred, and then left at room temperature. After storing for 24 hours with occasional stirring, the bacterial cells were filtered out, and the methanol extract was mixed with the same volume of water, and then added to an ODS adsorption column (manufactured by Nippon Millipore, column volume 778, methanol/water = 171). (equilibration). Using the eluate (methanol/water = 2/1), both fractions 1, 2 and lit were sequentially obtained, and by concentration and recrystallization operations, Nal of the present substance corresponding to each fraction: 5.0 mg,
Na2: 8.7 mH and Na3: loOmg were obtained.
実施例3
(1)実施例1で得られた培養濾液のうち5Q中に、そ
のL/10体積に相当する吸着剤アンバーライトXAD
−7を加え、時々振とうしながら4時間室温にて吸着
処理した。吸引濾過により、吸着剤を濾別し、精製水で
洗浄した後、吸着剤体積の2倍量に相当する20%メタ
ノール水溶液で洗浄した。その後、吸着剤体積の3倍量
に相当する80%メタノ−’−qEy’水溶液で溶出さ
せ、溶出液を減圧濃縮した後。Example 3 (1) In 5Q of the culture filtrate obtained in Example 1, adsorbent Amberlite XAD corresponding to L/10 volume was added
-7 was added, and adsorption treatment was carried out at room temperature for 4 hours with occasional shaking. The adsorbent was separated by suction filtration, washed with purified water, and then washed with a 20% aqueous methanol solution equivalent to twice the volume of the adsorbent. Thereafter, it was eluted with an 80% methanol-'-qEy' aqueous solution corresponding to 3 times the volume of the adsorbent, and the eluate was concentrated under reduced pressure.
精製水に溶解させた。はぼ100%近い活性が回収でき
た。Dissolved in purified water. Almost 100% activity was recovered.
(2)次に、CM−トヨバール650Mカラム〔東ソー
製、カラム体積533mff 、 0.05M酢酸−酢
酸アンモニウム(pH4,0)で平衡化〕にpl+4.
0に調整した試料溶液を吸着させ、0.05M酢酸−酢
酸アンモニウム(ρ116.0)で溶出させた。活性画
分は溶出液のpH5,0から溶出してきた。活性画分の
肥満細胞脱顆粒抑制活性は25,250ユニツトであっ
た。(2) Next, pl+4.
A sample solution adjusted to 0 was adsorbed and eluted with 0.05M acetic acid-ammonium acetate (ρ116.0). The active fraction was eluted from the eluate at pH 5.0. The mast cell degranulation inhibitory activity of the active fraction was 25,250 units.
(3)さらに上記(2)の活性画分を、ρII !1
、0に調整した後、DEAE−トヨパール650Mカラ
ム〔東ソー製、カラム体積179mQ、0.05M酢酸
アンモニウム−アンモニア水でpl−19,0に平衡化
〕に、吸着させ、0.05M酢酸アンモニウム−アンモ
ニア水(pH7,5)で溶出させた。この活性画分の活
性は、16,500ユニツ1へであった。(3) Furthermore, the active fraction of (2) above is added to ρII! 1
, 0, and then adsorbed on a DEAE-Toyopearl 650M column [manufactured by Tosoh, column volume 179 mQ, equilibrated with 0.05M ammonium acetate-ammonia water to pl-19.0], and 0.05M ammonium acetate-ammonia Elution was performed with water (pH 7.5). The activity of this active fraction was 16,500 units.
(4)さらに、MCIゲル(CIIP −20P、三菱
化成W)を充填した吸着カラム(カラム体積40mff
)に、前記(3)で得られた活性画分を吸着させ、20
%アセト°日Jトリル水溶液で洗浄後、40%アセトニ
トリル水溶液で溶出させ、減圧濃縮して白色物質を得た
。(4) Furthermore, an adsorption column (column volume 40 mff) packed with MCI gel (CIIP-20P, Mitsubishi Kasei W)
) to adsorb the active fraction obtained in (3) above, and
After washing with a 40% acetonitrile aqueous solution, the mixture was eluted with a 40% acetonitrile aqueous solution and concentrated under reduced pressure to obtain a white substance.
得られた物質をメタノールに溶解させ、IIPLCにて
分離した。この場合の分離条件は次の通りである。The obtained material was dissolved in methanol and separated by IIPLC. The separation conditions in this case are as follows.
カ ラ ム:ヌクレオシル5C8充填、直径10mm、
長さ250mm
使用溶媒ニアセトニトリル/酢酸アンモニウム緩衝液(
0,01M、 、115.0)=35/65流 速:
4mQ/分
検 出:紫外波長:350 n mにおける吸光度d
1q定試料濃度=0.2mg/d
注入量:200μQ/回
上記条件にて物質Nnl、Nα2及びNα3に該当する
両分を分取し、減圧濃縮して物質Nnl:1.1mg、
Nα2:1.5mg及びNn3:10mgを得た。Column: filled with Nucleosil 5C8, diameter 10mm,
Length 250mm Solvent used: Niacetonitrile/ammonium acetate buffer (
0.01M, , 115.0) = 35/65 flow rate:
4mQ/min Detection: Ultraviolet wavelength: Absorbance d at 350 nm
1q constant sample concentration = 0.2 mg/d Injection amount: 200 μQ/time Under the above conditions, fractionate both substances corresponding to Nnl, Nα2 and Nα3, and concentrate under reduced pressure to obtain Substance Nnl: 1.1 mg,
Nα2: 1.5 mg and Nn3: 10 mg were obtained.
実施例4
(1)物質Ncil、Nn2及びNa3をそれぞれ約1
..5Bを正−1\’= 1
−r61’%、 N=1.76%ト、 物質Nn2:C
=57.70%、 1I=7.57%1、+3.ン乙
N=1.65%、物質Na 3 : C=58T8−h
’A、l−1=8.10%、N=1.86%とatり定
され、それぞれ、C15llsiOxtN (理論値C
=57.27%、H= 7 、76%、 N=1.71
%)C4゜11G50□iN(理論値:C夕22謔
=5−7−i70%、I+=7.87%、 N=1.6
8%)、 C,、HGsOl、N(C=58゜88に、
H=8.03%、 N=1.72%)の組成をもつも
のであると明らかになった。Example 4 (1) About 1 each of the substances Ncil, Nn2 and Na3
.. .. 5B is positive -1\'= 1 -r61'%, N=1.76%, substance Nn2:C
=57.70%, 1I=7.57%1, +3. N = 1.65%, substance Na3: C = 58T8-h
'A, l-1 = 8.10%, N = 1.86%, respectively, C15llsiOxtN (theoretical value C
=57.27%, H=7, 76%, N=1.71
%) C4゜11G50□iN (Theoretical value: C=5-7-i70%, I+=7.87%, N=1.6
8%), C,, HGsOl, N (C=58°88,
It was revealed that the composition was 8.03% (H = 8.03%, N = 1.72%).
(2)物質Nα1. Nα2及びNα3について、その
質量分析を行った。 FAB−MS法による測定結果は
、物質Nα1は、 (Mill)”=782.36とな
り、C3g+(、,0,SN(M=781゜39)と判
明した。物質&2は、 (Mill)”=796.47
となり、C4゜)I、、01.N(M=795.40)
と判明した。物質Nα3は、 (Mill)”=780
.45となり、C4,)1..01.N(M=779.
41)と判明した。元素分析法の値はそれぞれ2水塩(
211□0)であると推定された。(2) Substance Nα1. Mass spectrometry was performed on Nα2 and Nα3. The measurement results by FAB-MS method revealed that substance Nα1 was (Mill)”=782.36, and C3g+(,,0,SN (M=781°39). Substance &2 was (Mill)”= 796.47
So, C4゜)I,,01. N (M=795.40)
It turned out to be. The substance Nα3 is (Mill)”=780
.. 45, C4,)1. .. 01. N (M=779.
41). The elemental analysis values are for dihydrate (
211□0).
(3)物質Nα1. Nα2及びNα3をメタノールに
溶解し紫外線吸収スペクトル分析を行った。その結果は
物質Nal、&2及び廃3はいずれも302nm、 3
16nm。(3) Substance Nα1. Nα2 and Nα3 were dissolved in methanol and subjected to ultraviolet absorption spectroscopy. The result is that the substance Nal, &2 and waste 3 are both 302 nm, 3
16nm.
331nm及び349nmに極大波長を示すペンタエン
構造であることが明らかとなり、吸収の強さはE(1%
。It was revealed that the pentaene structure has maximum wavelengths at 331 nm and 349 nm, and the absorption strength is E (1%
.
4(316r+n+)、1375(331nm)及び1
388 (349nm)となり、物質Nn2では、34
4 (302nm)、700 (316nm)、112
2(33Lnm)及び1144 (349nm)となり
、物質Na3では、:162(302nm) 、 76
0(316nm)、1210 (331nm)及び12
32(349nm)となった。4 (316r+n+), 1375 (331 nm) and 1
388 (349 nm), and in the material Nn2, it is 34
4 (302nm), 700 (316nm), 112
2 (33Lnm) and 1144 (349nm), and for the substance Na3: 162 (302nm), 76
0 (316 nm), 1210 (331 nm) and 12
32 (349 nm).
(4)物質Nnl、Nα2及びNα3をそれぞれ約10
μg計りとり、臭化カリウムと混合して錠剤をつくり、
にB「タブレット法による赤外線吸収スペクトル分析法
を行った。その結果、各物質とも、3380cn+−’
1700cm−”、1560am−’、 1390cm
−1,1070cm−’及び10010O5”に吸収を
示し、ポリエン物質としての特徴を示していた。(4) About 10 each of the substances Nnl, Nα2 and Nα3
Measure out μg and mix with potassium bromide to make tablets.
Infrared absorption spectrum analysis using the tablet method was conducted on B. As a result, each substance had a
1700cm-", 1560am-', 1390cm
-1,1070 cm-' and 10010 O5'', indicating the characteristics of a polyene material.
(5)物質Nα1、Nα2及びN(13をそれぞれ重水
素置換ジメチルホルムアミド(oMr−d)もしくは重
水素置換ジメチルスルホキシド(DMSO−d)に溶解
して核磁気共鳴スペクトル分析を行った。1■核磁気共
鳴スペクトル 13 c M磁気共鳴スペクトル、 1
3C−DEPT測定及びJl−J(シフト相関二次元核
磁気共鳴スペクトル分析を行い、各物質の構造は前記一
般式%式%
Nα3の場合、R’=C113、P=11、)+3=l
+を示すものであることを決定した。(5) Substances Nα1, Nα2, and N(13) were dissolved in deuterium-substituted dimethylformamide (oMr-d) or deuterium-substituted dimethyl sulfoxide (DMSO-d), respectively, and nuclear magnetic resonance spectroscopy was performed. 1. Nuclear Magnetic Resonance Spectrum 13 c M Magnetic Resonance Spectrum, 1
3C-DEPT measurement and Jl-J (shift correlation two-dimensional nuclear magnetic resonance spectrum analysis were performed, and the structure of each substance was determined by the general formula %Nα3, R'=C113, P=11,)+3=l
It was determined that it indicates +.
実施例5
(1)ウィスター系雌性ラット(体重150〜250
g )を脱血致死させ、腹腔内にタイロード液を20m
Q注入し、腹部を約2分間軽くマツサージした。開腹
後腹水を採取し、4℃にて150Xg、10分間の条件
で遠心分離し、沈澱する細胞を集めた。この細胞をタイ
ロード液2mQに懸濁させ、比重1.068に調整した
牛血清アルブミン含有生理食塩水4mQに重層し、4℃
、1100Xの条件で12分間遠心分離後、沈澱する細
胞を集めた。タイロード液で2回洗浄した後、0.2%
牛血清アルブミンを含むタイロート液に肥満細胞が約1
06個/mQとなるように懸濁させ、肥満細胞浮遊液を
得た。Example 5 (1) Wistar female rats (body weight 150-250
g) The animal was bled to death, and 20 m of Tyrode's solution was administered intraperitoneally.
Q was injected, and the abdomen was lightly massaged for about 2 minutes. Ascites fluid was collected after laparotomy and centrifuged at 150×g for 10 minutes at 4° C. to collect precipitated cells. These cells were suspended in 2 mQ of Tyrode's solution, overlaid on 4 mQ of physiological saline containing bovine serum albumin adjusted to a specific gravity of 1.068, and placed at 4°C.
After centrifugation for 12 minutes at 1100X, the precipitated cells were collected. After washing twice with Tyrode's solution, 0.2%
There are approximately 1 mast cell in Tyroth's solution containing bovine serum albumin.
The cells were suspended at a concentration of 0.06 cells/mQ to obtain a mast cell suspension.
(2)被験化合物を含む生理食塩水zOμQと肥満細胞
浮遊液20μQを10分間37℃にて反応させ、最終濃
度Iμg/mAとなるようにコンパウンド48/80溶
後1分間水冷した後、1,500Xg、4分間の条件で
遠心し、上澄と細胞とを分離した。上澄に含まれるヒス
タミンを0ndaらのIIPLC法(llirochi
ma J、Mad。(2) Physiological saline zOμQ containing the test compound and 20μQ mast cell suspension were reacted at 37°C for 10 minutes, and after dissolving compound 48/80 to a final concentration of Iμg/mA, cooling with water for 1 minute, 1. The supernatant and cells were separated by centrifugation at 500×g for 4 minutes. Histamine contained in the supernatant was analyzed using the IIPLC method of Onda et al.
ma J, Mad.
Sci 、第27巻、93〜07ページ、1978年)
により定量することにより脱顆粒を測定した。この場合
、肥満細胞脱顆粒抑制活性は以下の式により算出した6
A;細胞をコンパウンド48/80とのみ反応させた時
に遊離されたヒスタミン量
B;被験化合物を細胞と反応させた後、コンパウンド4
8/80を加えてさらに反応させた時に遊離されたヒス
タミン量
C;細胞を緩衝液(もしくは生理食塩水)とのみ反応さ
せた時にTi離されたヒスタミン量脱顆粒誘発剤として
は、コンパウンド48/80(シグマ社!Iilりの他
、コンカナバリンA、イオノフオアA23187はじめ
一般に知られている任意の薬剤を用いることができる。Sci, Vol. 27, pp. 93-07, 1978)
Degranulation was measured by quantification. In this case, the mast cell degranulation inhibitory activity was calculated by the following formula 6
A; Amount of histamine released when cells were reacted only with compound 48/80 B; Compound 4 was released after reacting the test compound with cells.
Amount of histamine released when cells were further reacted with 8/80 C; Amount of histamine released by Ti when cells were reacted only with buffer solution (or physiological saline) As a degranulation inducing agent, Compound 48/ 80 (Sigma Co., Ltd.), concanavalin A, ionophore A23187, and any other commonly known drugs can be used.
・・1・・・1.;
m−“被験化合物の濃度を種々変えて測定を行い1本8
1り定系でlμg/−のコンパウンド4g/80により
誘発される肥満細胞脱顆粒を50%抑制する化合物の濃
度(IC,。〕値を求めた。また、コンパウンド48/
80の存在しない状態や、コレステロールを添加した状
態など各種の状態や、コレステロールを添加した状態な
ど各種の条件下で本物質を肥満細胞に対する機能調節作
用の測定も合せて行い、その結果は以下に示すように、
本物質には1強い肥満細胞機能調節作用をもつことが認
められた。...1...1. m-“Measurements were made with various concentrations of the test compound.
The concentration (IC, ) of the compound that inhibits 50% of the mast cell degranulation induced by lμg/- of Compound 4g/80 was determined in a constant system.
We also measured the functional regulatory effect of this substance on mast cells under various conditions such as the absence of 80, the addition of cholesterol, and the addition of cholesterol.The results are as follows. As shown,
This substance was found to have a strong mast cell function regulating effect.
なお、本211!I定系で1μg/mAのコンパウンド
48/80により誘発される肥満細胞脱顆粒作用を50
%抑制する化合物の濃度を1単位/−〔1ユニツl−/
m1ll )とした。In addition, book 211! The mast cell degranulation effect induced by compound 48/80 at 1 μg/mA was
% inhibiting compound concentration by 1 unit/- [1 unit l-/
m1ll).
(3)lμに10112のコンパウンド48/80の誘
発する肥満細胞脱顆粒作用に対して物質Nα1、Nα2
及びNa3の示した作用は次の通りであった。(3) Substances Nα1 and Nα2 against the mast cell degranulation effect induced by Compound 48/80 of 10112 on lμ
The effects of Na3 and Na3 were as follows.
(3) −(i)
物質Nα1.Na2及びNα3は低濃度領域では肥満細
胞脱顆粒抑制作用を示し、そのIC,、値は、物質−2
′九’l:3.6μg/mfA、物質)lIa2:1.
8μバ/成、物質Nα3:1.0μg/−であった。(3) -(i) Substance Nα1. Na2 and Nα3 exhibit an inhibitory effect on mast cell degranulation at low concentrations, and their IC values are similar to that of substance-2.
'9'l: 3.6 μg/mfA, substance) lIa2: 1.
The content was 8 μg/min, and the substance Nα3 was 1.0 μg/−.
(3) −(ii)
物質Nα1. Nα2及びNα3は高濃度領域では単独
で肥満細胞脱顆粒作用を示し1本作用は、反応液のカル
シウムイオン濃度を約1mM以」二にした時に発現し、
反応液のカルシウムイオン濃度がOに近い時は発現しな
いというカルシウムイオン依存性を示した。(3) -(ii) Substance Nα1. Nα2 and Nα3 independently exert a mast cell degranulation effect in the high concentration range, and the single effect is expressed when the calcium ion concentration of the reaction solution is lowered to about 1mM or more.
When the calcium ion concentration of the reaction solution was close to O, calcium ion dependence was not expressed.
(3) −(iii)
反応液にコレステロールを一定濃度(約2μg/mQ)
以上加−えることにより、上記(3) −(i)及び(
3) −(ii)の作用はコレステロールに対して濃度
依存的に減少した。(3) -(iii) Add cholesterol to the reaction solution at a constant concentration (approximately 2 μg/mQ)
By adding the above, the above (3) - (i) and (
3) The effect of -(ii) decreased in a concentration-dependent manner on cholesterol.
実施例6
物質Nalを100mg;t−tりとり、ジメチルスル
ホキシド2mQに溶解した後、無水メタノール0.2d
を加えて希釈した。0.3モル濃度のジアゾメタンを含
むテトラヒドロフラン1mQをこれに加えて4℃にて約
2分間反応させ、エステル化を行った。反応液に一無ズ
エチルエーテル20+++9を加えて沈殿する物質を遠
心にて集め、少量の無水エチルエーテルにて洗浄後、同
溶媒にて再結晶化操作を行い、物質Nalのメチルエス
テル(前記一般式(1)においてR1=C11J、R”
=11.1セ’=CII:Iを示すもの)、72mgを
得た。Example 6 Take 100 mg of the substance Nal, dissolve it in 2 mQ of dimethyl sulfoxide, and then add 0.2 d of anhydrous methanol.
was added and diluted. 1 mQ of tetrahydrofuran containing 0.3 molar concentration of diazomethane was added thereto, and the mixture was reacted at 4° C. for about 2 minutes to perform esterification. Nal-free ethyl ether 20+++9 was added to the reaction solution, and the precipitated material was collected by centrifugation, washed with a small amount of anhydrous ethyl ether, and then recrystallized with the same solvent. In formula (1), R1=C11J, R”
=11.1ce'=CII:I), 72 mg was obtained.
メチルエステルの同定は質量分析及び核磁気共鳴スペク
1−ル分析により行った。The methyl ester was identified by mass spectrometry and nuclear magnetic resonance spectrum analysis.
以上のように、本発明により、特定のポリエン物質が肥
満X1■胞機能調節作用を有することが明らかにされた
。As described above, the present invention has revealed that a specific polyene substance has an effect of regulating obese X1 cell function.
特許出願人 工業技術院長 飯 塚 幸 三指定代
理人 工業技術院微生物工業技術研究所1長鈴木智雄Patent Applicant: Yukio Iizuka, Director, Agency of Industrial Science and Technology Designated Agent: Tomoo Suzuki, Director, Institute of Microbial Technology, Agency of Industrial Science and Technology
Claims (1)
素原子、水酸基、アルキル基、アルコキシ基又はケトン
基、R^3は水素原子、塩形成性カチオン又はアルキル
基を示す)(2)請求項1のポリエン物質からなる肥満
細胞機能調節剤。(1) A polyene substance represented by the following general formula. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R^1 is a hydrogen atom or an alkyl group, R^2 is a hydrogen atom, hydroxyl group, alkyl group, alkoxy group, or ketone group, R^3 is a hydrogen atom or a salt (2) A mast cell function regulator comprising the polyene substance according to claim 1.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP1055862A JPH064669B2 (en) | 1988-03-09 | 1989-03-08 | Polyene substance and obesity function regulator |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP63-55580 | 1988-03-09 | ||
JP5558088 | 1988-03-09 | ||
JP1055862A JPH064669B2 (en) | 1988-03-09 | 1989-03-08 | Polyene substance and obesity function regulator |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH021498A true JPH021498A (en) | 1990-01-05 |
JPH064669B2 JPH064669B2 (en) | 1994-01-19 |
Family
ID=26396468
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP1055862A Expired - Lifetime JPH064669B2 (en) | 1988-03-09 | 1989-03-08 | Polyene substance and obesity function regulator |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPH064669B2 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0654802A (en) * | 1991-10-21 | 1994-03-01 | Symbiosis Corp | Apparatus for operation |
US6302616B1 (en) | 1999-09-01 | 2001-10-16 | Olympus Optical Co., Ltd. | Rotation mechanism including rotation shaft and fixed member with welding structure, and producing method of the same |
-
1989
- 1989-03-08 JP JP1055862A patent/JPH064669B2/en not_active Expired - Lifetime
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0654802A (en) * | 1991-10-21 | 1994-03-01 | Symbiosis Corp | Apparatus for operation |
US6302616B1 (en) | 1999-09-01 | 2001-10-16 | Olympus Optical Co., Ltd. | Rotation mechanism including rotation shaft and fixed member with welding structure, and producing method of the same |
Also Published As
Publication number | Publication date |
---|---|
JPH064669B2 (en) | 1994-01-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP3800205B1 (en) | Esterified selenium polysaccharide and preparation method and use thereof | |
JPS6310953B2 (en) | ||
JPH021498A (en) | Polyene substance and agent for controlling mast cell function | |
JP3024864B2 (en) | Ellagic acid glycoside and method for producing the same | |
CA1181394A (en) | Water-soluble cholesterol derivative | |
JPS61293993A (en) | Novel fluorescent substance, production thereof and pharmaceutical | |
WO2004016216A2 (en) | Imidazole alkaloids from lepidium meyenii and methods of usage | |
CZ242094A3 (en) | Process for preparing pure oxytetracycline and intermediate for the preparation thereof | |
JPH0415770B2 (en) | ||
JP4087589B2 (en) | Method for producing camptothecin | |
JP2809573B2 (en) | New lysophosphatidylinositol and its production method | |
JP3030896B2 (en) | WB968 substance group and production method thereof | |
JPS5918037B2 (en) | New physiologically active substance anthglutin and its production method | |
JPS6020000B2 (en) | New antibiotic Y-16482 substance and its manufacturing method | |
JPS61227528A (en) | Agent for controlling function of mastocyte | |
JPH03145492A (en) | Pyrroloquinolinequinone ester | |
JP3707936B2 (en) | Gastric ulcer and duodenal ulcer | |
JPH08501687A (en) | Novel natural products cyclamenol and chemical derivatives | |
EP4183792A1 (en) | 3-deoxy-2-ketonic acid nitrogen-containing derivative, preparation method therefor, and use thereof | |
CN113024617A (en) | N-aryl sulfonamide-N-beta-D-glucopyranose diamide compounds and application thereof | |
JPH09110781A (en) | Isobenzofuranone compound and its homolog | |
JPH09241226A (en) | New derivative from antibiotic ab5366 and their production and agricultural/horticultural germicide | |
JPH06503327A (en) | 13-demethyl FR-900506 derivative and its use as an immunosuppressant | |
JPH1129465A (en) | Antitumor agent | |
JPS62270527A (en) | Antitumor agent containing 4181-2 substance and its derivative |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EXPY | Cancellation because of completion of term |