CAS 66-76-2|Dicoumarol
Introduction：Basic information about CAS 66-76-2|Dicoumarol, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
| Common Name | Dicoumarol | ||
|---|---|---|---|
| CAS Number | 66-76-2 | Molecular Weight | 336.295 |
| Density | 1.6±0.1 g/cm3 | Boiling Point | 620.7±55.0 °C at 760 mmHg |
| Molecular Formula | C19H12O6 | Melting Point | 290-292 °C(lit.) |
| MSDS | ChineseUSA | Flash Point | 231.9±25.0 °C |
| Symbol | GHS07, GHS08, GHS09 | Signal Word | Danger |
Names
| Name | Dicoumarol |
|---|---|
| Synonym | More Synonyms |
Dicoumarol BiologicalActivity
| Description | Dicoumarol is an inhibitor of both NAD(P)H:quinone oxidoreductase 1 (NQO1) and PDK1 with IC50s of 0.37 and 19.42 μM, respectively. |
|---|---|
| Related Catalog | Signaling Pathways >>Metabolic Enzyme/Protease >>PDHKResearch Areas >>CancerNatural Products >>Phenylpropanoids |
| Target | IC50: 0.37 μM (NQO1)[1], 19.42 μM (PDK1)[2] |
| In Vitro | Dicoumarol is an inhibitor of both NAD(P)H:quinone oxidoreductase 1 (NQO1) and PDK1 with IC50s of 0.37±0.15 and 19.42±0.032 μM, respectively. The PDK1 activity is inhibited by Dicoumarol in a dose-dependent manner. The enzymatic activity of PDK1 is reduced by approximately 94% when treated with 200 μM Dicoumarol. Dicoumarol decreases the p-PDHA1 level by 26% (100 μM Dicoumarol) and by 72% (200 μM Dicoumarol), with no statistical difference in the total PDHA1 level. Both 100 μM and 200 μM Dicoumarol markedly induce apoptosis of SKOV3 cells. Similarly, flow cytometric analysis of annexin V+PI+ cells reveals that 100 μM and 200 μM Dicoumarol treatments generate approximately 20.87% and 24.94% apoptotic cells, respectively, significantly higher than vehicle treatment[2]. It is also observed that treatment of MCF-7-TAMR cells with Dicoumarol, a known NQO1 inhibitor, reverses their tamoxifen-resistance phenotype[3]. |
| In Vivo | Dichloroacetate (DCA) at 100 mg/kg, Dicoumarol at 30 mg/kg, and Dicoumarol at 50 mg/kg all significantly reduce tumor volume and decrease tumor weight, when compare to tumors from control or vehicle groups. Total caspase-3 and total anti-poly (ADP-ribose) polymerase (PARP) are significantly decreased in Dicoumarol-treated SKOV3 xenografts, when compare to tumors from the control or vehicle group[2]. |
| Cell Assay | The in vitro cell viability is examined using the standard MTT assay. SKOV3 or A2780 cells are seeded in 96-well plates at 8000 cells/well. The next day, increasing concentrations of Dicoumarol (DIC) are added into each well, and the plate is incubated for 24 h. Then, 10 μL of 10 mg/mL MTT reagent in phosphate-buffered saline (PBS) is added into each well, and the plate is incubated for an additional 4 h. The formazan crystals are dissolved in 150 μL of DMSO, and after the plate is shaken for 5 min, the optical density at 570 nm is recorded by the reader[2]. |
| Animal Admin | Twenty five female BALB/c-nu mice aged 5 to 6 weeks old and weighing approximately 15 g each are used. A total of 1×107 SKOV3 cells are subcutaneously injected into the upper flank. After 10 days, when the tumor volume reaches approximately 100 mm3, the nude mice are randomized into five groups (n=5/group) and are given the following treatments intraperitoneally (i.p.) every other day, for a total of 12 days: control group, administered with 0.2 mL of 0.9% NaCl; vehicle group, administered with 1 mM NaOH; dichloroacetate (DCA) group, administered with 100 mg/kg DCA; Dicoumarol (DIC)-30 group, administered with 30 mg/kg Dicoumarol; and Dicoumarol-50 group, administered with 50 mg/kg Dicoumarol. The body weights and tumor volumes of each mouse are monitored every other day until sacrifice (on day 12 after the initial treatment)[2]. |
| References | [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. |
Chemical & Physical Properties
| Density | 1.6±0.1 g/cm3 |
|---|---|
| Boiling Point | 620.7±55.0 °C at 760 mmHg |
| Melting Point | 290-292 °C(lit.) |
| Molecular Formula | C19H12O6 |
| Molecular Weight | 336.295 |
| Flash Point | 231.9±25.0 °C |
| Exact Mass | 336.063385 |
| PSA | 100.88000 |
| LogP | 3.55 |
| Vapour Pressure | 0.0±1.9 mmHg at 25°C |
| Index of Refraction | 1.731 |
| InChIKey | DOBMPNYZJYQDGZ-UHFFFAOYSA-N |
| SMILES | O=c1oc2ccccc2c(O)c1Cc1c(O)c2ccccc2oc1=O |
Toxicological Information
CHEMICAL IDENTIFICATION |
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)
Safety Information
| Symbol | GHS07, GHS08, GHS09 |
|---|---|
| Signal Word | Danger |
| Hazard Statements | H302-H372-H411 |
| Precautionary Statements | P260-P301 + P312 + P330 |
| Personal Protective Equipment | Eyeshields;Faceshields;Gloves;type P2 (EN 143) respirator cartridges |
| Hazard Codes | T,N |
| Risk Phrases | R22;R48/25;R51/53 |
| Safety Phrases | 37-45-61 |
| RIDADR | UN 2811 6.1/PG 3 |
| WGK Germany | 3 |
| RTECS | GN7875000 |
| Packaging Group | III |
| Hazard Class | 6.1(b) |
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Synonyms
| Acavyl |
| Antitrombosin |
| Coumarin, 3,3'-methylenebis[4-hydroxy- |
| Dufalone |
| Cumid |
| Trombosan |
| 3,3'-Methylenebis[4-hydroxycoumarin] |
| 4-hydroxy-3-[(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl]-2H-chromen-2-one |
| Baracoumin |
| Dicoumal |
| 3,3'-methanediylbis(4-hydroxy-2H-chromen-2-one) |
| Temparin |
| Dicuman |
| 3,3’-methylenebis(4-hydroxy-2H-1-benzopyran-2-one) |
| 4-hydroxy-3-[(4-hydroxy-2-oxochromen-3-yl)methyl]chromen-2-one |
| 2H-1-Benzopyran-2-one, 3,3'-methylenebis[4-hydroxy- |
| 3,3’-methylenebis(4-hydroxycoumarin) |
| Dicumarol |
| Bishydroxycoumarin |
| 3,3'-Methylene-bis(4-hydroxycoumarin) |
| EINECS 200-632-9 |
| Dicoumarol |
| 3,3’-methylenebis(4-hydroxy-2H-chromen-2-one) |
| Dicoumarin |
| 3,3'-Methylenebis(4-hydroxy-2H-chromen-2-one) |
| 3,3'-Methylenebis[4-hydroxy-2H-1-benzopyran-2-one] |
| Acadyl |
| 3,3’-methylenebis[4-hydroxy-2H-1-benzopyran-2-one] |
| Dicumarine |
| MFCD00006857 |
| Kumoran |
| Melitoxin |
| 3,3'-methylenebis(4-hydroxycoumarin) |
