Coumestrol

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Coumestrol
Coumestrol.png
Identifiers
CAS number 479-13-0 YesY
PubChem 5281707
ChemSpider 4445024 YesY
UNII V7NW98OB34 YesY
KEGG C10205 YesY
ChEBI CHEBI:3908 N
ChEMBL CHEMBL30707 YesY
Jmol-3D images Image 1
Image 2
Properties
Molecular formula C15H8O5
Molar mass 268.22 g mol−1
Melting point 385 °C (725 °F; 658 K) (decomp)[1]
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N (verify) (what is: YesY/N?)
Infobox references

Coumestrol is a natural organic compound in the class of phytochemicals known as coumestans. It has garnered research interest because of its estrogenic activity and its prevalence in some foods, such as soybeans.

Coumestrol was first identified by E. M. Bickoff in alfalfa in 1957.[2] It has since be found in a variety of legumes, soybeans, brussels sprouts, and spinach. Clover and soybeans have the highest concentrations.[3]

Coumestrol is a phytoestrogen, mimicking the biological activity of estrogens. Coumestrol has about the same binding affinity for the ER-β estrogen receptor as 17β-estradiol, but much less affinity than 17α-estradiol, although the estrogenic potency of coumestrol at both receptors is much less than that of 17β-estradiol.[4]

The chemical shape of coumestrol orients its two hydroxy groups in the same position as the two hydroxy groups in estradiol, allowing it to inhibit the activity of aromatase and hydroxysteroid dehydrogenase.[5] These enzymes are involved in the biosynthesis of steroid hormones, and inhibition of these enzymes results in the modulation of hormone production.[3]

Recent work by the Pappo group showed a new synthetic approach based on aerobic iron oxidative cross-coupling of phenols with ethyl 2-benzoylacetate derivatives. A preliminary SAR study was performed in which the coumestrol derivatives were found to inhibit the proliferation of estrogen-dependent MCF-7 breast cancer cells but not of estrogen-independent MDA-MB-321 breast cancer cells. This suggests that these compounds act through the ERs. In addition, the importance of the 3-hydroxy group for the anti-proliferative activity was demonstrated, and an improved estrogenic activity was found when the 9-hydroxy group found in the natural product was replaced with an acetamide group. Whereas the inhibitory activity of 9-acetamidocoumestrol of MCF7 cell proliferation was found to be of the same order of magnitude as that of the natural compound coumestrol, 8-acet-amidocoumestrol was about 8 times more active than Coumestrol.[6]

References[edit]

  1. ^ Bickoff, E. M.; Livingston, A. L.; Witt, S. C.; Knuckles, B. E.; Guggolz, Jack; Spencer, R. R. (1964). "Isolation of coumestrol and other phenolics from alfalfa by countercurrent distribution". Journal of Pharmaceutical Sciences 53 (12): 1496–9. doi:10.1002/jps.2600531213. PMID 14255129. 
  2. ^ E. M. Bickoff, A. N. Booth, R. L. Lyman, A. L. Livingston, C. R. Thompson, and F. Deeds (1957). "Coumestrol, a New Estrogen Isolated from Forage Crops". Science 126 (3280): 969–970. doi:10.1126/science.126.3280.969-a. PMID 13486041. 
  3. ^ a b Amr Amin and Michael Buratovich (2007). "The Anti-Cancer Charm of Flavonoids: A Cup-of-Tea Will Do!". Recent Patents on Anti-Cancer Drug Discovery 2 (2): 109–117. doi:10.2174/157489207780832414. PMID 18221056. 
  4. ^ Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der Burg B, Gustafsson JA (1998). "Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta". Endocrinology 139 (10): 4252–4263. doi:10.1210/endo.139.10.6216. PMID 9751507. 
  5. ^ Blomquist CH, Lima PH, Hotchkiss JR (2005). "Inhibition of 3a-hydroxysteoid dehydogenase (3a-HSD) activity of human lung microsomes by genistein, daidzein, coumestrol and C18-, C19- and C21 hydroxysteroids and ketosteroids". Steroids 70 (8): 507–514. doi:10.1016/j.steroids.2005.01.004. PMID 15894034. 
  6. ^ Kshirsagar, U.A, Parnes, R, Goldshtein, H., Ofir, R., Zarivach,R., Pappo,D (2013). "Aerobic iron-based cross-dehydrogenative coupling enables efficient diversity-oriented synthesis of coumestrol-based selective estrogen receptor modulators.". Chem.-Eur.J 19 (40): 13575–13583. doi:10.1002/chem.201300389.