Deguelin

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Deguelin
IUPAC name (7aS,13aS)-13,13a-Dihydro-9,10-
dimethoxy-3,3-dimethyl-3H-bis[1]
benzopyrano [3,4-b:6’,5’-3]
pyran-7(7aH)-one
Other names Deguelin; 3H-Bis(1)b​enzopyrano​
(3,4-b:6',​5'-e)pyran​-7(7aH)-on​e,
13,13a-​dihydro-9,​10-dimetho​xy-3,3-
dim​ethyl-, (7​aS,13aS)-; 3H-Bis(1)
b​enzopyrano​(3,4-b:6',​5'-e)pyran​-
7(7aH)-on​e, 13,13a-​dihydro- 9,​
10-dimetho​xy-3,3-dim​ethyl-, (7​aS-cis)-
Identifiers
CAS number [522-17-8]
SMILES O=C2c5c(O[C@@H]3COc1cc(OC)c(OC)
cc1[C@H]23)c4\C=C/C(Oc4cc5)(C)C
InChI 1/C2 ​3H22O6/c1-​23(2)8-7-1​2-15
(29-23​)6-5-13-21​(24)20-14-​9-17(25-3)​ 18(26-4)10​-16(14)27-​11-
19(20)2​8-22(12)13​/h5-10,19-​20H,11H2,1​ -4H3/t19-,​20+/m1/s1
Properties
Molecular formula C23H22O6
Molar mass 394.42 g/mol
Melting point

171 °C
Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)
Infobox disclaimer and references

Deguelin is a derivative of rotenone. Both are compounds classified as rotenoids of the flavonoid family and are naturally occurring insecticides. They can be produced by extraction from several plant species belonging to three genera of the Fabaceae or Legume family, Lonchocarpus, Derris, or Tephrosia.

Cubé resin, the root extract from Cubé (Lonchocarpus utilis) and from Barbasco (Lonchocarpus urucu), is used as a commercial insecticide and piscicide (fish poison). The major active ingredients are rotenone and deguelin. Although "organic" (produced by nature) cubé resin is no longer considered environmentally safe.

Contents

[edit] Pharmacokinetics

[1]

  • Mean residence time (MRT) = 6.98 h
  • Terminal half-life (t1/2(gamma)) = 9.26 h
  • Area under the curve (AUC) = 57.3 ng h/ml
  • Total clearance (Cl) = 4.37 l/h per kg
  • Apparent volume of distribution (V) = 3.421 l/kg
  • Volume of distribution at steady-state (Vss) = 30.46 l/kg
  • Tissue distributions after i.v. (intravenous) administration: heart > fat > mammary gland > colon > liver > kidney > brain > lung.
  • Tissue distributions after i.g. (intragastric) administration: perirenal fat > heart > mammary gland > colon > kidney > liver > lung > brain > skin.
  • Elimination: Within 5 days of i.g. administration, about 58.1% of the [3H]deguelin was eliminated via the feces and 14.4% via the urine. Approximately 1.7% of unchanged deguelin was found in the feces, and 0.4% in the urine.

[edit] Deguelin and Anti-cancer activity

Deguelin displays anti-cancer activity by inhibiting the growth of pre-cancerous and cancerous cells[2] - particularly for lung cancer[3]. So far the compound has shown no toxic effects on normal cells. However, high doses of deguelin are suspected of having negative effects on the heart, lungs and nerves. The molecular mechanisms include the induction of apoptosis, mediatated through AKT/PKB signaling pathways in malignant and premaligant human bronchial epithelia (HBE) cells, with only minimal effects on nomal HBE cells. Deguelin inhibits AKT by both Phosphoinositol-3-phosphate kinase (PI3K)-dependent and PI3K-independent pathways.

[edit] Deguelin and Parkinson's disease

Research has shown a correlation between intravenous deguelin and Parkinson's disease in rats[4]. The study does not suggest that deguelin exposure is responsible for Parkinson's disease in humans, but is consistent with the belief that chronic exposure to environmental toxins can increase the likelihood of the disease.

[edit] References

  1. ^ Udeani GO, Zhao GM, Shin YG, Kosmeder JW 2nd, Beecher CW, Kinghorn AD, Moriarty RM, Moon RC, Pezzuto JM. Pharmacokinetics of deguelin, a cancer chemopreventive agent in rats. Cancer Chemother Pharmacol. 2001 Mar;47(3):263-8. [PMID 11320671].
  2. ^ Lee HY. Molecular mechanisms of deguelin-induced apoptosis in transformed human bronchial epithelial cells. Biochem Pharmacol. 2004 Sep 15;68(6):1119-24. [PMID 15313408].
  3. ^ Chun KH, Kosmeder JW 2nd, Sun S, Pezzuto JM, Lotan R, Hong WK, Lee HY. Effects of deguelin on the phosphatidylinositol 3-kinase/Akt pathway and apoptosis in premalignant human bronchial epithelial cells. J Natl Cancer Inst. 2003 Feb 19;95(4):291-302. [PMID 12591985].
  4. ^ Caboni P, Sherer TB, Zhang N, Taylor G, Na HM, Greenamyre JT, Casida JE. Rotenone, deguelin, their metabolites, and the rat model of Parkinson's disease. Chem Res Toxicol. 2004 Nov;17(11):1540-8. [PMID 15540952.]

[edit] External links