Molecular Weight (MW)

394.42

Formula

C23H22O6

CAS No.

522-17-8

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 78 mg/mL (197.8 mM)

Water: <1 mg/mL

Ethanol: 78 mg/mL (197.8 mM)

Other info

Chemical Name: (7aS,13aS)-9,10-dimethoxy-3,3-dimethyl-13,13a-dihydro-3H-pyrano[2,3-c:6,5-f']dichromen-7(7aH)-one.

InChi Key: ORDAZKGHSNRHTD-UXHICEINSA-N

InChi Code: InChI=1S/C23H22O6/c1-23(2)8-7-12-15(29-23)6-5-13-21(24)20-14-9-17(25-3)18(26-4)10-16(14)27-11-19(20)28-22(12)13/h5-10,19-20H,11H2,1-4H3/t19-,20+/m1/s1

SMILES Code: O=C1[C@]2([H])[C@](COC3=CC(OC)=C(OC)C=C32)([H])OC4=C5C=CC(C)(C)OC5=CC=C14

Synonyms

(-)-Deguelin, (-)-cis-Deguelin

In Vitro

In vitro activity: Deguelin downregulates Akt phosphorylation in leukaemia cell lines with an active PI3K/Akt axis. At 10 or 100 nmol/l, deguelin is effective in inhibiting Akt phosphorylation. Total Akt expression is unchanged by deguelin. Moreover, deguelin does not affect the expression or the phosphorylation levels of either p44/42 or p38 MAP kinases in U937 cells. Deguelin increases sensitivity of human leukaemia cells to chemotherapeutic drugs. Deguelin dephosphorylates Akt and increases cytarabine sensitivity of AML blasts but not of CB CD34+. Deguelin, when employed for 24 h at 10 nmol/l, causes an S phase arrest of U937 cells, with interference of progression to G2/M phase. While employed alone up to a concentration of 10 nmol/l for 24 h, Deguelin does not significantly increase the apoptotic rate of U937 cells.

Cell Assay: Flow cytometric analysis of cell cycle in response to deguelin. Cells are incubated with the indicated concentrations of deguelin for 24 h, then analysed for DNA content and for the percentage of cells in specific phases of the cell cycle by means of PI staining, whereas for detection of apoptotic cells the Annexin-FITC staining was employed. For this reason, the sum of apoptotic cells plus cells in various phases of the cell cycle exceeds 100%.

In Vivo

Deguelin (2 or 4 mg/kg body weight), when injected intraperitoneally, reduced the in vivo tumor growth of MDA-MB-231 cells transplanted subcutaneously in athymic mice. Moreover it was nontoxic as evident from daily observations on mobility, food and water consumption and comparison of bodyweight and other visceral organ weights with those in control animals at the termination of the study. In the colon cancer xenograft model, the volume of the tumor treated withdeguelin was significantly lower than that of the control, and the apoptotic index for deguelin-treated mice was much higher.

Animal model

A/J mice

Formulation & Dosage

Dissolved in corn oil; 5.0 or 10.0 mg/kg ; i.p. injection

References

Br J Haematol. 2005 Jun;129(5):677-86; J Pharmacol Exp Ther. 2008 Feb;324(2):643-7; Mol Clin Oncol. 2013 Mar;1(2):215-219.