JP2020147509A - 抗がん剤 - Google Patents
抗がん剤 Download PDFInfo
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- JP2020147509A JP2020147509A JP2019044662A JP2019044662A JP2020147509A JP 2020147509 A JP2020147509 A JP 2020147509A JP 2019044662 A JP2019044662 A JP 2019044662A JP 2019044662 A JP2019044662 A JP 2019044662A JP 2020147509 A JP2020147509 A JP 2020147509A
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- CFMYXEVWODSLAX-UHFFFAOYSA-N tetrodotoxin Natural products C12C(O)NC(=N)NC2(C2O)C(O)C3C(CO)(O)C1OC2(O)O3 CFMYXEVWODSLAX-UHFFFAOYSA-N 0.000 description 1
- 229950010357 tetrodotoxin Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 150000003667 tyrosine derivatives Chemical class 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
で表される化合物、その塩、又は該化合物若しくはその塩の溶媒和物。
で表される化合物の生産能を有する、ハロスフェリア科(Halosphaeriaceae)に属する真菌。
で表される化合物の製造方法。
本発明は、その一態様において、一般式(1):
で表される化合物が挙げられる。
本発明の化合物、その塩、及び該化合物若しくはその塩の溶媒和物は、公知の方法に従って又は準じて化学合成することができる。或いは、本発明の化合物の生産能を有するハロスフェリア科(Halosphaeriaceae)に属する真菌の培養物を回収する工程を含む方法によっても製造することができる。特に、後者の方法は、原料である真菌を培養によって大量調製できるので、効率性の観点から好ましい。以下にこの製造方法について説明する。
本発明の有効成分は、細胞増殖抑制作用(細胞増殖阻害作用)、抗がん作用を有する。このため、本発明の有効成分は、医薬、試薬、化粧品、食品添加剤、食品組成物(健康食品、健康増進剤、栄養補助食品(サプリメントなど)を包含する)等、多様な分野において利用することができる。より具体的には、本発明の有効成分は、細胞増殖抑制剤、抗がん剤、がん治療剤等に利用することができる。すなわち、本発明は、その一態様において、本発明の有効成分を含有する、医薬、試薬、化粧品、食品添加剤、食品組成物細胞増殖抑制剤、抗がん剤、がん治療剤(本明細書において、これらをまとめて「本発明の剤」と示すこともある。)等に関する。
7月大阪府泉南郡岬町沿岸において採取した海藻ウミトラノオの表面から真菌を単離し、独立行政法人製品評価技術基盤機構(NITE)の特許微生物寄託センター(NPMD)に、2019年3月5日付けで寄託した(ハロスフェリア科OUPS-135D-4株、特許微生物寄託センター受領番号:NITE AP−02908)。
実施例1で単離された真菌を、80Lの液体培地(組成:1.0% D-グルコース、1.0% 麦芽エキス、0.05% ペプトン/海水 pH7.5)に播種し、4週間27℃で培養した。
旋光度[α]D 25 105.7
HREIMS: 615.2380 Δ+0.4 mmu [M+H]+
IR νmax (liquid) cm-1 : 3393, 2930, 2862, 1752, 1706, 1657, 1612
UV λmax nm (log ε): 196.5 (4.6), 225.5 (4.1)
1H NMRスペクトル (600 MHz, CDCl3) : 図1に示す。
13C NMRスペクトル (150 MHz, CDCl3): 図2に示す。
被検細胞(マウスリンパ性白血病細胞(P388))を培地中に懸濁した(1×104 cells/mL)。次に、被検化合物(実施例2で得られた化合物A、又は5-フルオロウラシル)をジメチルスルホキシドで溶解し、培地で希釈した(被検化合物の培地中終濃度:100μM、10μM、及び1μM)。調製した被検化合物溶液と細胞懸濁液を96ウェルマイクロプレートに100μLずつ播種した(200μL/ウェル)。5%CO2雰囲気下37℃で3日間培養した。培養後、チアゾイルブルーテトラゾリウム/リン酸緩衝液(6mg/mL、25μL)を加え細胞を染色してから、20%ドデシル硫酸ナトリウム(50μL)によりホルマゾンを溶解し、マイクロプレートリーダーで吸光度を測定した。濃度ごとに細胞の増殖率を計算し、50%細胞増殖阻害濃度を求めた。結果を表1に示す。
Claims (12)
- 一般式(1):
で表される化合物、その塩、又は該化合物若しくはその塩の溶媒和物。 - 前記R1が−OR11であり、前記R2及びR3が共に水素原子であり、前記R4がアルキル基であり、且つ前記R5が分岐鎖状炭化水素基である、請求項1に記載の化合物、その塩、又は該化合物若しくはその塩の溶媒和物。
- 前記一般式(1)で表される化合物が、式(1a):
- 請求項1〜3のいずれかに記載の化合物、その塩、又は該化合物若しくはその塩の溶媒和物を含有する、医薬。
- 請求項1〜3のいずれかに記載の化合物、その塩、又は該化合物若しくはその塩の溶媒和物を含有する、細胞増殖抑制剤。
- 前記細胞ががん細胞である、請求項5に記載の細胞増殖抑制剤。
- 前記細胞が白血病細胞である、請求項5又は6に記載の細胞増殖抑制剤。
- 請求項1〜3のいずれかに記載の化合物、その塩、又は該化合物若しくはその塩の溶媒和物を含有する、抗がん剤。
- 請求項1〜3のいずれかに記載の化合物、その塩、又は該化合物若しくはその塩の溶媒和物を含有する、白血病治療剤。
- 一般式(1):
で表される化合物の生産能を有する、ハロスフェリア科(Halosphaeriaceae)に属する真菌。 - ハロスフェリア科OUPS-135D-4株(特許微生物寄託センター受領番号:NITE AP−02908)である、真菌。
- 請求項10又は11に記載の真菌の培養物を回収する工程を含む、一般式(1):
で表される化合物の製造方法。
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2002060890A1 (fr) * | 2001-02-01 | 2002-08-08 | Mercian Corporation | Nouvelles substances physiologiquement actives |
WO2008081568A1 (ja) * | 2006-12-27 | 2008-07-10 | National University Corporation Hokkaido University | 新規マクロライド化合物 |
WO2012086114A1 (ja) * | 2010-12-24 | 2012-06-28 | 国立大学法人東北大学 | 抗がん作用を有するマクロライド化合物 |
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Publication number | Priority date | Publication date | Assignee | Title |
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WO2002060890A1 (fr) * | 2001-02-01 | 2002-08-08 | Mercian Corporation | Nouvelles substances physiologiquement actives |
WO2008081568A1 (ja) * | 2006-12-27 | 2008-07-10 | National University Corporation Hokkaido University | 新規マクロライド化合物 |
WO2012086114A1 (ja) * | 2010-12-24 | 2012-06-28 | 国立大学法人東北大学 | 抗がん作用を有するマクロライド化合物 |
Non-Patent Citations (1)
Title |
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化学と教育, vol. 43巻11号, JPN6023009028, 1995, pages 691 - 694, ISSN: 0005005462 * |
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