| Identification | Back Directory | [Name]
DEGUELIN | [CAS]
522-17-8 | [Synonyms]
DEGUELIN
Ccris 8104
()-Deguelin
(-)-DEGUELIN
(7as-cis)-oxy-
Deguelin (6CI)
(-)-cis-Deguelin
12a-DEOXYTEPHROSIN
(-)-DEGUELIN;(-)-CIS-DEGUELIN
3h-bis(1)benzopyrano(3,4-b:6’,5’-e)pyran-7(7ah)-one,13,13a-dihydro-9,10-dimeth
(7aS,13aS)-9,10-Dimethoxy-3,3-dimethyl-13,13a-dihydro-3H-pyrano[2,3-c:6,5-f']dichromen-7(7aH)-one
3,3-Dimethyl-9,10-dimethoxy-7,7aα,13,13aα-tetrahydro-3H-bis[1]benzopyrano[3,4-b:6',5'-e]pyran-7-one
(7aS)-3,3-Dimethyl-9,10-dimethoxy-7,7aα,13,13aα-tetrahydro-3H-bis[1]benzopyrano[3,4-b:6',5'-e]pyran-7-one
(7AS,13AS)-13,13A-DIHYDRO-9,10-DIMETHOXY-3,3-DIMETHYL-3H-BIS[1]BENZOPYRANO[3,4-B:6',5'-E]PYRAN-7(7AH)-ONE
(7aS,13aS)-13,13a-Dihydro-9,10-dimethoxy-3,3-dimethyl-(3H)-bis[1]benzopyrano[3.4-b.6'.5'-e]pyran-7(7aH)-one
3H-Bis(1)benzopyrano(3,4-B:6',5'-E)pyran-7(7ah)-one, 13,13A-dihydro-9,10-dimethoxy-3,3-dimethyl-, (7as-cis)-
3H-Bis(1)benzopyrano(3,4-B:6',5'-E)pyran-7(7ah)-one, 13,13A-dihydro-9,10-dimethoxy-3,3-dimethyl-, (7as,13as)- | [EINECS(EC#)]
200-258-5 | [Molecular Formula]
C23H22O6 | [MDL Number]
MFCD01740600 | [MOL File]
522-17-8.mol | [Molecular Weight]
394.42 |
| Chemical Properties | Back Directory | [Melting point ]
85-87 °C(lit.)
| [alpha ]
D27 -97.2° (c = 0.2 in benzene) | [Boiling point ]
560.1±50.0 °C(Predicted) | [density ]
1?+-.0.06 g/cm3(Predicted) | [storage temp. ]
-20°C | [solubility ]
DMSO: >10 mg/mL
| [form ]
solid
| [color ]
white to yellow
| [Optical Rotation]
[α]/D -70 to -80°, c = 0.2 in methanol | [Stability:]
Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months. |
| Hazard Information | Back Directory | [Description]
Rotenoids, deriving from the flavonoid family of compounds, act as chemopreventive agents that inhibit NADH:ubiquinone oxidoreductase activity and suppress phorbol ester-induced ornithine decarboxylase (ODC) activity.1 The rotenoid compound deguelin, originally isolated from the bark of M. sericea (Leguminosae) to be used as an insecticide and fish poison, has chemopreventive and chemosensitizing effects in models of skin, mammary, colon, and lung carcinogenesis.2,3,4 Deguelin inhibits cell growth (IC50 = <10-8 M), blocks PI3K/Akt activation, suppresses COX-2 expression, and induces apoptosis in premalignant and squamous human bronchial epithelial (HBE) cells without affecting normal HBE cells.2,5 At 6 mg/kg, deguelin induces Parkinson’s disease-like symptoms in rats after six days of subcutaneous infusion and therefore may also serve as a useful model for Parkinson’s disease research.6 | [Uses]
antineoplastic, antiviral, insecticide, ornithine decarboxylate inhibitor | [Uses]
Deguelin exhibits potent apoptotic and antiangiogenic activities in a variety of transformed cells and cancer cells. Deguelin also exhibits potent tumor suppressive effects in xenograft tumor models
for many human cancers. | [Definition]
ChEBI: Deguelin is a rotenone that is 13,13a-dihydro-3H-chromeno[3,4-b]pyrano[2,3-h]chromen-7(7aH)-one substituted by methoxy groups at positions 9 and 10, and by two methyl groups at position 3 (the 7aS,13aS-stereoisomer). It exists in abundant quantities in the bark, roots, and leaves of the Leguminosae family of plants and reported to exert anti-tumour effects in various cancers. It has a role as an apoptosis inducer, an antineoplastic agent, a plant metabolite, an angiogenesis inhibitor, an antiviral agent, a mitochondrial NADH:ubiquinone reductase inhibitor, an anti-inflammatory agent and an EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor. It is a member of rotenones, an aromatic ether, an organic heteropentacyclic compound and a diether. | [Biological Activity]
Anticancer and antiviral agent; chemopreventive and pro-apoptotic. Inhibits phorbol ester-induced ornithine decarboxylase and NADH:ubiquinone oxidoreductase activities (IC 50 values are 11 and 6.9 nM respectively). Inhibits PI 3-kinase and reduces pAkt levels in pre-malignant and malignant human bronchial epithelial cells. Active in vivo . | [Biochem/physiol Actions]
Deguelin is a natural rotenoid compound present abundantly in barks, leaves, seeds, and roots of the plants belonging to the Leguminosae family. Deguelin has been studied as a therapeutic agent against the skin, lung cancer, and mammary tumorigenesis. | [Synthesis]
Synthesis of (7aS,13aS)-9,10-dimethoxy-3,3-dimethyl-13,13a-dihydro-9-hydroxy-2,3-dimethoxy-8-(3-methyl-2-buten-1-yl)[1]benzopyrano[3,4-B][1]benzopyridoxol-12(6H)-ones as (6AS,12AS)-6A,12A-dihydropyrano[2,4-B][1]benzopyridoxol-12(6H)-ones 3H-pyrano[2,3-c:6,5-f']dibenzopyran-7(7aH)-one in the following general steps:
1. phenylselenyl chloride (68 mg, 0.35 mmol) was added under argon protection to an anhydrous dichloromethane containing (6AS,12AS)-6A,12A-dihydro-9-hydroxy-2,3-dimethoxy-8-(3-methyl-2-buten-1-yl)[1 ]benzopyrano[3,4-B][1 ]benzopyridoxol-12(6H)-one (128 mg, 0.32 mmol) in an anhydrous dichloromethane solution (4.0 mL) at a reaction temperature of -30 °C with stirring for 10 min.
2. Slowly warm to room temperature and continue stirring for 2 hours followed by 1 hour.
3. remove the solvent under pressure, dissolve the residue in tetrahydrofuran (4.0 mL) and add 30% aqueous hydrogen peroxide solution (0.06 mL) at 0 °C.
4. The reaction mixture was stirred to room temperature, during which the progress of the reaction was monitored by thin layer chromatography (TLC).
5. Upon completion of the reaction, the organic layer was separated by adding ethyl acetate (8.0 mL) and water (4.0 mL).
6. The organic layer was washed sequentially with 5% aqueous sodium bicarbonate and brine, dried over magnesium sulfate, filtered and concentrated.
7. The crude product was purified by fast column chromatography (ethyl acetate:hexane=1:2) to afford (7aS,13aS)-9,10-dimethoxy-3,3-dimethyl-13,13a-dihydro-3H-pyrano[2,3-c:6,5-f']dibenzopyran-7(7aH)-one in the form of a yellowish solid in a yield of 61% (78 mg).
Product characterization data:
1H-NMR (CDCl3, 400 MHz) δ 7.72 (d, 1H, J = 8.7 Hz), 6.77 (s, 1H), 6.62 (d, 1H, J = 10.0 Hz), 6.43 (s, 1H), 6.43 (d, 1H, J = 8.7 Hz), 5.53 (d, 1H, J = 10.0 Hz), 4.89 (m, 1H ), 4.61 (dd, 1H, J = 12.0, 3.1 Hz), 4.17 (d, 1H, J = 12.0 Hz), 3.82 (d, 1H, J = 4.1 Hz), 3.78 (s, 3H), 3.75 (s, 3H), 1.43 (s, 3H), 1.36 (s, 3H).
13C-NMR (CDCl3, 100 MHz) δ 189.2, 160.0, 156.9, 149.4, 147.4, 143.8, 128.6, 128.5, 115.7, 112.7, 111.4, 110.4, 109.1, 104.7, 100.9, 77.6, 72.4, 66.2, 56.3, 55.8, 44.3, 28.4, 28.1.
HRMS (FAB) calculated value C23H23O6 (M+H+): 395.1495, measured: 395.1495. | [target]
FAK | ROS | Caspase | Akt | ERK | PARP | EGFR | p53 | p21 | MMP(e.g.TIMP) | PKC | PI3K | MEK | NOS | COX | JNK | p38MAPK | ROCK | NF-kB | p65 | VEGFR | [References]
1) Chun et al. (2003), Effects of deguelin on the phosphatidylinositol 3- kinase/Akt pathway and apoptosis in premalignant human bronchial epithelial cells; J. Natl. Cancer Inst., 95 291
2) Kang et al. (2012), Deguelin, an AKT Inhibitor, Down-Regulates NFκB Signaling and Induces Apoptosis in Colon Cancer Cells and Inhibits Tumor Growth in Mice; Dig. Dis. Sci.,?57 2873
3) Lee et al. (2004), Molecular mechanisms of deguelin-induced apoptosis in transformed human bronchial epithelial cells; Biochem. Pharmacol., 68 1119
4) Ito et al. (2004), Cancer chemopreventive activity of rotenoids from Derris trifoliata; Planta Med., 70 8 |
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