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双羟香豆素

双羟香豆素用途

Dicoumarol 是 NAD(P)H: 醌氧化还原酶 1 (NQO1) 和 PDK1 的抑制剂,IC50 值分别为 0.37 和 19.42 μM。

双羟香豆素名称

[ CAS 号 ]:
66-76-2

[ 中文名 ]:
双香豆素

[ 英文名 ]:
Dicoumarol

[中文别名 ]:

[英文别名 ]:

Acavyl
Antitrombosin
Coumarin, 3,3'-methylenebis[4-hydroxy-
Dufalone
Cumid
Trombosan
3,3'-Methylenebis[4-hydroxycoumarin]
Baracoumin
Dicoumal
3,3'-methanediylbis(4-hydroxy-2H-chromen-2-one)

双羟香豆素生物活性

[ 描述 ]:

Dicoumarol 是 NAD(P)H: 醌氧化还原酶 1 (NQO1) 和 PDK1 的抑制剂,IC50 值分别为 0.37 和 19.42 μM。

[ 相关类别 ]:

信号通路 >> 代谢酶/蛋白酶 >> PDHK

研究领域 >> 癌症

天然产物 >> 苯丙酸类

[ 靶点 ]

IC50: 0.37 μM (NQO1)[1], 19.42 μM (PDK1)[2]

[体外研究]

Dicoumarol是NAD(P)H：醌氧化还原酶1(NQO1)和PDK1的抑制剂,IC50分别为0.37±0.15和19.42±0.032μM。 Dicoumarol以剂量依赖性方式抑制PDK1活性。当用200μMDicoumarol处理时,PDK1的酶活性降低约94％。双香豆素使p-PDHA1水平降低26％(100μMDicoumarol)和72％(200μMDicoumarol),总PDHA1水平无统计学差异。 100μM和200μM双香豆素均显着诱导SKOV3细胞凋亡。同样,膜联蛋白V + PI +细胞的流式细胞术分析显示,100μM和200μMDicoumarol处理分别产生约20.87％和24.94％的凋亡细胞,显着高于载体处理[2]。还观察到用已知的NQO1抑制剂Dicoumarol处理MCF-7-TAMR细胞可逆转他们的他莫昔芬抗性表型[3]。

[体内研究]

与对照组或赋形剂组的肿瘤相比,100mg/kg的二氯乙酸酯(DCA),30mg/kg的双香豆素和50mg/kg的双香豆素均显着降低肿瘤体积并降低肿瘤重量。与来自对照或载体组的肿瘤相比,Dicoumarol处理的SKOV3异种移植物中总caspase-3和总抗多聚(ADP-核糖)聚合酶(PARP)显着降低[2]。

[细胞实验]

使用标准MTT测定检查体外细胞活力。将SKOV3或A2780细胞以8000个细胞/孔接种在96孔板中。第二天，将增加浓度的双香豆素（DIC）加入每个孔中，并将板孵育24小时。然后，将10μL10mg/ mL MTT试剂的磷酸盐缓冲盐水（PBS）加入每个孔中，并将板再孵育4小时。将甲crystals晶体溶解在150μLDMSO中，并且在将板振荡5分钟后，由读数器记录570nm处的光密度[2]。

[动物实验]

使用25只年龄为5至6周龄，体重约15g的雌性BALB / c-nu小鼠。将总共1×107个SKOV3细胞皮下注射到上胁腹中。 10天后，当肿瘤体积达到约100mm 3时，将裸鼠随机分成5组（n = 5 /组），每隔一天腹膜内（ip）给予以下治疗，总共12天：对照组，给予0.2mL 0.9％NaCl;载体组，给予1mM NaOH;二氯乙酸（DCA）组，给予100mg / kg DCA;双香豆素（DIC）-30组，给予30mg / kg双香豆素;和Dicoumarol-50组，给予50mg / kg Dicoumarol。每隔一天监测每只小鼠的体重和肿瘤体积直至处死（在初始治疗后第12天）[2]。

[参考文献]

[1]. Bian J, et al. Affinity-based small fluorescent probe for NAD(P)H:quinone oxidoreductase 1 (NQO1). Design, synthesis and pharmacological evaluation. Eur J Med Chem. 2017 Feb 15;127:828-839.

[2]. Zhang W, et al. Dicumarol inhibits PDK1 and targets multiple malignant behaviors of ovarian cancer cells. PLoS One. 2017 Jun 15;12(6):e0179672.

[3]. Fiorillo M, et al. Mitochondrial "power" drives tamoxifen resistance: NQO1 and GCLC are new therapeutic targets in breast cancer. Oncotarget. 2017 Mar 2;8(12):20309-20327.

[相关活性小分子]

VER-246608 | AZD7545

双羟香豆素物理化学性质

[ 密度 ]:
1.6±0.1 g/cm3

[ 沸点 ]:
620.7±55.0 °C at 760 mmHg

[ 熔点 ]:
290-292 °C(lit.)

[ 分子式 ]:
C₁₉H₁₂O₆

[ 分子量 ]:
336.295

[ 闪点 ]:
231.9±25.0 °C

[ 精确质量 ]:
336.063385

[ PSA ]:
100.88000

[ LogP ]:
3.55

[ 外观性状 ]:
白色粉末

[ 蒸汽压 ]:
0.0±1.9 mmHg at 25°C

[ 折射率 ]:
1.731

[ 储存条件 ]:
库房通风低温干燥,与食品原料分开储运

双羟香豆素MSDS

详细MSDS(安全技术说明书)

双羟香豆素毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: GN7875000

CHEMICAL NAME :: Coumarin, 3,3'-methylenebis(4-hydroxy-

CAS REGISTRY NUMBER :: 66-76-2

BEILSTEIN REFERENCE NO. :: 0335444

LAST UPDATED :: 199706

DATA ITEMS CITED :: 23

MOLECULAR FORMULA :: C19-H12-O6

MOLECULAR WEIGHT :: 336.31

WISWESSER LINE NOTATION :: T66 BOVJ EQ D1- DT66 BOVJ EQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 250 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: SMWOAS Schweizerische Medizinische Wochenschrift. (Schwabe & Co., Steintorst 13, 4010 Basel, Switzerland) V.50- 1920- Volume(issue)/page/year: 83,471,1953

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 52 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Olfaction) - ulcerated nasal septum Gastrointestinal - ulceration or bleeding from large intestine

REFERENCE :: PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 50,228,1942

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 233 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Olfaction) - ulcerated nasal septum Gastrointestinal - ulceration or bleeding from large intestine

REFERENCE :: PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 50,228,1942

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 91 mg/kg

TOXIC EFFECTS :: Cardiac - other changes Vascular - pulse pressure increase

REFERENCE :: DIPHAH Dissertationes Pharmaceuticae. (Warsaw, Poland) V.1-17, 1949-65. For publisher information, see PJPPAA. Volume(issue)/page/year: 17,163,1965

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 50 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: 85GDA2 "CRC Handbook of Antibiotic Compounds," Vols.1- , Berdy, J., Boca Raton, FL, CRC Press, 1980- Volume(issue)/page/year: 8(1),360,1982

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 42 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: AEPPAE Naunyn-Schmiedeberg's Archiv fuer Experimentelle Pathologie und Pharmakologie. (Berlin, Ger.) V.110-253, 1925-66. For publisher information, see NSAPCC. Volume(issue)/page/year: 222,107,1954

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 40 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: 27ZIAQ "Drug Dosages in Laboratory Animals - A Handbook," Rev. ed., Barnes, C.D., and L.G. Eltherington, Berkeley, Univ. of California Press, 1973 Volume(issue)/page/year: -,57,1973

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 75 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: AEPPAE Naunyn-Schmiedeberg's Archiv fuer Experimentelle Pathologie und Pharmakologie. (Berlin, Ger.) V.110-253, 1925-66. For publisher information, see NSAPCC. Volume(issue)/page/year: 222,107,1954

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 22 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: AEPPAE Naunyn-Schmiedeberg's Archiv fuer Experimentelle Pathologie und Pharmakologie. (Berlin, Ger.) V.110-253, 1925-66. For publisher information, see NSAPCC. Volume(issue)/page/year: 222,107,1954

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 59 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Olfaction) - ulcerated nasal septum Gastrointestinal - ulceration or bleeding from large intestine

REFERENCE :: PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 50,228,1942 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 112 mg/kg/30D-C

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - acute pulmonary edema Blood - hemorrhage Related to Chronic Data - death

REFERENCE :: PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 50,228,1942

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 180 mg/kg/30D-C

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - acute pulmonary edema Blood - hemorrhage Related to Chronic Data - death

REFERENCE :: PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 50,228,1942

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 127 mg/kg/7D-I

TOXIC EFFECTS :: Related to Chronic Data - death

REFERENCE :: DIPHAH Dissertationes Pharmaceuticae. (Warsaw, Poland) V.1-17, 1949-65. For publisher information, see PJPPAA. Volume(issue)/page/year: 17,163,1965

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 150 mg/kg/30D-I

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - acute pulmonary edema Blood - hemorrhage Related to Chronic Data - death

REFERENCE :: PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 50,228,1942

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 20 mg/kg/4D-I

TOXIC EFFECTS :: Related to Chronic Data - death

REFERENCE :: DIPHAH Dissertationes Pharmaceuticae. (Warsaw, Poland) V.1-17, 1949-65. For publisher information, see PJPPAA. Volume(issue)/page/year: 17,163,1965

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 4200 ug/kg/42D-I

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - acute pulmonary edema Blood - hemorrhage Related to Chronic Data - death

REFERENCE :: PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 50,228,1942 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 110 mg/kg

SEX/DURATION :: female 31-40 week(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Effects on Newborn - stillbirth Reproductive - Effects on Newborn - other neonatal measures or effects

REFERENCE :: AJOGAH American Journal of Obstetrics and Gynecology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1920- Volume(issue)/page/year: 57,965,1949

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Unreported

DOSE :: 28 mg/kg

SEX/DURATION :: female 28-30 week(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

REFERENCE :: AJOGAH American Journal of Obstetrics and Gynecology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1920- Volume(issue)/page/year: 77,1135,1959 *** REVIEWS *** TOXICOLOGY REVIEW PLMJAP Pahlavi Medical Journal. (Shiraz, Iran) V.1-9, 1970-78. Volume(issue)/page/year: 6,160,1975 TOXICOLOGY REVIEW AJOGAH American Journal of Obstetrics and Gynecology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1920- Volume(issue)/page/year: 77,1135,1959 TOXICOLOGY REVIEW NYSJAM New York State Journal of Medicine. (Medical Soc. of the State of New York, POB 5405, Lake Success, NY 11042) V.1- 1901- Volume(issue)/page/year: 64,493,1964 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 83988 No. of Facilities: 33 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 297 (estimated)

双羟香豆素安全信息

[ 符号 ]:

GHS07, GHS08, GHS09

[ 信号词 ]:
Danger

[ 危害声明 ]:
H302-H372-H411

[ 警示性声明 ]:
P260-P301 + P312 + P330

[ 个人防护装备 ]:
Eyeshields;Faceshields;Gloves;type P2 (EN 143) respirator cartridges

[ 危害码 (欧洲) ]:
T,N

[ 风险声明 (欧洲) ]:
R22;R48/25;R51/53

[ 安全声明 (欧洲) ]:
37-45-61

[ 危险品运输编码 ]:
UN 2811 6.1/PG 3

[ WGK德国 ]:
3

[ RTECS号 ]:
GN7875000

[ 包装等级 ]:
III

[ 危险类别 ]:
6.1(b)

双羟香豆素合成路线

详细合成路线

双羟香豆素文献

Sulfation modulates the cell uptake, antiradical activity and biological effects of flavonoids in vitro: An examination of quercetin, isoquercitrin and taxifolin.

Bioorg. Med. Chem. 23 , 5402-9, (2015)

Quercetin 3'-O-sulfate is one of the main metabolites of the natural flavonoid quercetin in humans. This study was designed to prepare quercetin 3'-O-sulfate (1), isoquercitrin 4'-O-sulfate (2) and ta...

Comparative Study of 17-AAG and NVP-AUY922 in Pancreatic and Colorectal Cancer Cells: Are There Common Determinants of Sensitivity?

Transl. Oncol. 7(5) , 590-604, (2014)

The use of heat shock protein 90 (Hsp90) inhibitors is an attractive antineoplastic therapy. We wanted to compare the effects of the benzoquinone 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanesp...

Impaired vitamin K recycling in uremia is rescued by vitamin K supplementation.

Kidney Int. 86(2) , 286-93, (2014)

In chronic kidney disease, vitamin K-dependent proteins, including the calcification inhibitor matrix Gla protein, are largely uncarboxylated indicating that functional vitamin K deficiency may contri...

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