Stilbestrol

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Stilbestrol
Stilbestrol.svg
Names
Preferred IUPAC name
4,4′-[(E)-Ethene-1,2-diyl]diphenol
Other names
Dihydroxystilbene; 4,4'-Dihydroxystilbene, 4,4'-stilbenediol
Identifiers
3D model (JSmol)
ChemSpider
PubChem CID
UNII
  • InChI=1S/C14H12O2/c15-13-7-3-11(4-8-13)1-2-12-5-9-14(16)10-6-12/h1-10,15-16H/b2-1+
    Key: XLAIWHIOIFKLEO-OWOJBTEDSA-N
  • C1=CC(=CC=C1C=CC2=CC=C(C=C2)O)O
  • c1cc(ccc1/C=C/c2ccc(cc2)O)O
Properties
C14H12O2
Molar mass 212.24388 g/mol
−130·10−6 cm3/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Stilbestrol, or stilboestrol, also known as 4,4'-dihydroxystilbene or 4,4'-stilbenediol, is a stilbenoid nonsteroidal estrogen [1] and the parent compound of a group of more potent nonsteroidal estrogen derivatives that includes, most notably, diethylstilbestrol (DES). [1] [2] [3] The term "stilbestrol" is often used incorrectly to refer to DES, but they are not the same compound. [2]

Contents

Stilbestrol itself is an active estrogen but is less potent than DES and other derivatives. [1]

Stilbestrol derivatives

The stilbestrol estrogenic drugs include the following:

Of the stilbestrol estrogens, diethylstilbestrol, hexestrol, and benzestrol are the most well-known. [4]

Mechanism of action

The stilbestrol estrogens bind with high affinity to both ERα and ERβ. [5]

Affinities of estrogen receptor ligands for the ERα and ERβ
Ligand Other names Relative binding affinities (RBA, %)a Absolute binding affinities (Ki, nM)aAction
ERα ERβ ERα ERβ
Estradiol E2; 17β-Estradiol1001000.115 (0.04–0.24)0.15 (0.10–2.08)Estrogen
Estrone E1; 17-Ketoestradiol16.39 (0.7–60)6.5 (1.36–52)0.445 (0.3–1.01)1.75 (0.35–9.24)Estrogen
Estriol E3; 16α-OH-17β-E212.65 (4.03–56)26 (14.0–44.6)0.45 (0.35–1.4)0.7 (0.63–0.7)Estrogen
Estetrol E4; 15α,16α-Di-OH-17β-E24.03.04.919Estrogen
Alfatradiol 17α-Estradiol20.5 (7–80.1)8.195 (2–42)0.2–0.520.43–1.2Metabolite
16-Epiestriol 16β-Hydroxy-17β-estradiol7.795 (4.94–63)50 ? ?Metabolite
17-Epiestriol 16α-Hydroxy-17α-estradiol55.45 (29–103)79–80 ? ?Metabolite
16,17-Epiestriol 16β-Hydroxy-17α-estradiol1.013 ? ?Metabolite
2-Hydroxyestradiol 2-OH-E222 (7–81)11–352.51.3Metabolite
2-Methoxyestradiol 2-MeO-E20.0027–2.01.0 ? ?Metabolite
4-Hydroxyestradiol 4-OH-E213 (8–70)7–561.01.9Metabolite
4-Methoxyestradiol 4-MeO-E22.01.0 ? ?Metabolite
2-Hydroxyestrone 2-OH-E12.0–4.00.2–0.4 ? ?Metabolite
2-Methoxyestrone 2-MeO-E1<0.001–<1<1 ? ?Metabolite
4-Hydroxyestrone 4-OH-E11.0–2.01.0 ? ?Metabolite
4-Methoxyestrone 4-MeO-E1<1<1 ? ?Metabolite
16α-Hydroxyestrone 16α-OH-E1; 17-Ketoestriol2.0–6.535 ? ?Metabolite
2-Hydroxyestriol 2-OH-E32.01.0 ? ?Metabolite
4-Methoxyestriol 4-MeO-E31.01.0 ? ?Metabolite
Estradiol sulfate E2S; Estradiol 3-sulfate<1<1 ? ?Metabolite
Estradiol disulfate Estradiol 3,17β-disulfate0.0004 ? ? ?Metabolite
Estradiol 3-glucuronide E2-3G0.0079 ? ? ?Metabolite
Estradiol 17β-glucuronide E2-17G0.0015 ? ? ?Metabolite
Estradiol 3-gluc. 17β-sulfate E2-3G-17S0.0001 ? ? ?Metabolite
Estrone sulfate E1S; Estrone 3-sulfate<1<1>10>10Metabolite
Estradiol benzoate EB; Estradiol 3-benzoate10 ? ? ?Estrogen
Estradiol 17β-benzoate E2-17B11.332.6 ? ?Estrogen
Estrone methyl ether Estrone 3-methyl ether0.145 ? ? ?Estrogen
ent-Estradiol 1-Estradiol1.31–12.349.44–80.07 ? ?Estrogen
Equilin 7-Dehydroestrone13 (4.0–28.9)13.0–490.790.36Estrogen
Equilenin 6,8-Didehydroestrone2.0–157.0–200.640.62Estrogen
17β-Dihydroequilin 7-Dehydro-17β-estradiol7.9–1137.9–1080.090.17Estrogen
17α-Dihydroequilin 7-Dehydro-17α-estradiol18.6 (18–41)14–320.240.57Estrogen
17β-Dihydroequilenin 6,8-Didehydro-17β-estradiol35–6890–1000.150.20Estrogen
17α-Dihydroequilenin 6,8-Didehydro-17α-estradiol20490.500.37Estrogen
Δ8-Estradiol 8,9-Dehydro-17β-estradiol68720.150.25Estrogen
Δ8-Estrone 8,9-Dehydroestrone19320.520.57Estrogen
Ethinylestradiol EE; 17α-Ethynyl-17β-E2120.9 (68.8–480)44.4 (2.0–144)0.02–0.050.29–0.81Estrogen
Mestranol EE 3-methyl ether ?2.5 ? ?Estrogen
Moxestrol RU-2858; 11β-Methoxy-EE35–435–200.52.6Estrogen
Methylestradiol 17α-Methyl-17β-estradiol7044 ? ?Estrogen
Diethylstilbestrol DES; Stilbestrol129.5 (89.1–468)219.63 (61.2–295)0.040.05Estrogen
Hexestrol Dihydrodiethylstilbestrol153.6 (31–302)60–2340.060.06Estrogen
Dienestrol Dehydrostilbestrol37 (20.4–223)56–4040.050.03Estrogen
Benzestrol (B2) –114 ? ? ?Estrogen
Chlorotrianisene TACE1.74 ?15.30 ?Estrogen
Triphenylethylene TPE0.074 ? ? ?Estrogen
Triphenylbromoethylene TPBE2.69 ? ? ?Estrogen
Tamoxifen ICI-46,4743 (0.1–47)3.33 (0.28–6)3.4–9.692.5SERM
Afimoxifene 4-Hydroxytamoxifen; 4-OHT100.1 (1.7–257)10 (0.98–339)2.3 (0.1–3.61)0.04–4.8SERM
Toremifene 4-Chlorotamoxifen; 4-CT ? ?7.14–20.315.4SERM
Clomifene MRL-4125 (19.2–37.2)120.91.2SERM
Cyclofenil F-6066; Sexovid151–152243 ? ?SERM
Nafoxidine U-11,000A30.9–44160.30.8SERM
Raloxifene –41.2 (7.8–69)5.34 (0.54–16)0.188–0.5220.2SERM
Arzoxifene LY-353,381 ? ?0.179 ?SERM
Lasofoxifene CP-336,15610.2–16619.00.229 ?SERM
Ormeloxifene Centchroman ? ?0.313 ?SERM
Levormeloxifene 6720-CDRI; NNC-460,0201.551.88 ? ?SERM
Ospemifene Deaminohydroxytoremifene0.82–2.630.59–1.22 ? ?SERM
Bazedoxifene – ? ?0.053 ?SERM
Etacstil GW-56384.3011.5 ? ?SERM
ICI-164,384 –63.5 (3.70–97.7)1660.20.08Antiestrogen
Fulvestrant ICI-182,78043.5 (9.4–325)21.65 (2.05–40.5)0.421.3Antiestrogen
Propylpyrazoletriol PPT49 (10.0–89.1)0.120.4092.8ERα agonist
16α-LE2 16α-Lactone-17β-estradiol14.6–570.0890.27131ERα agonist
16α-Iodo-E2 16α-Iodo-17β-estradiol30.22.30 ? ?ERα agonist
Methylpiperidinopyrazole MPP110.05 ? ?ERα antagonist
Diarylpropionitrile DPN0.12–0.256.6–1832.41.7ERβ agonist
8β-VE2 8β-Vinyl-17β-estradiol0.3522.0–8312.90.50ERβ agonist
Prinaberel ERB-041; WAY-202,0410.2767–72 ? ?ERβ agonist
ERB-196 WAY-202,196 ?180 ? ?ERβ agonist
Erteberel SERBA-1; LY-500,307 ? ?2.680.19ERβ agonist
SERBA-2 – ? ?14.51.54ERβ agonist
Coumestrol –9.225 (0.0117–94)64.125 (0.41–185)0.14–80.00.07–27.0Xenoestrogen
Genistein –0.445 (0.0012–16)33.42 (0.86–87)2.6–1260.3–12.8Xenoestrogen
Equol –0.2–0.2870.85 (0.10–2.85) ? ?Xenoestrogen
Daidzein –0.07 (0.0018–9.3)0.7865 (0.04–17.1)2.085.3Xenoestrogen
Biochanin A –0.04 (0.022–0.15)0.6225 (0.010–1.2)1748.9Xenoestrogen
Kaempferol –0.07 (0.029–0.10)2.2 (0.002–3.00) ? ?Xenoestrogen
Naringenin –0.0054 (<0.001–0.01)0.15 (0.11–0.33) ? ?Xenoestrogen
8-Prenylnaringenin 8-PN4.4 ? ? ?Xenoestrogen
Quercetin –<0.001–0.010.002–0.040 ? ?Xenoestrogen
Ipriflavone –<0.01<0.01 ? ?Xenoestrogen
Miroestrol –0.39 ? ? ?Xenoestrogen
Deoxymiroestrol –2.0 ? ? ?Xenoestrogen
β-Sitosterol –<0.001–0.0875<0.001–0.016 ? ?Xenoestrogen
Resveratrol –<0.001–0.0032 ? ? ?Xenoestrogen
α-Zearalenol –48 (13–52.5) ? ? ?Xenoestrogen
β-Zearalenol –0.6 (0.032–13) ? ? ?Xenoestrogen
Zeranol α-Zearalanol48–111 ? ? ?Xenoestrogen
Taleranol β-Zearalanol16 (13–17.8)140.80.9Xenoestrogen
Zearalenone ZEN7.68 (2.04–28)9.45 (2.43–31.5) ? ?Xenoestrogen
Zearalanone ZAN0.51 ? ? ?Xenoestrogen
Bisphenol A BPA0.0315 (0.008–1.0)0.135 (0.002–4.23)19535Xenoestrogen
Endosulfan EDS<0.001–<0.01<0.01 ? ?Xenoestrogen
Kepone Chlordecone0.0069–0.2 ? ? ?Xenoestrogen
o,p'-DDT –0.0073–0.4 ? ? ?Xenoestrogen
p,p'-DDT –0.03 ? ? ?Xenoestrogen
Methoxychlor p,p'-Dimethoxy-DDT0.01 (<0.001–0.02)0.01–0.13 ? ?Xenoestrogen
HPTE Hydroxychlor; p,p'-OH-DDT1.2–1.7 ? ? ?Xenoestrogen
Testosterone T; 4-Androstenolone<0.0001–<0.01<0.002–0.040>5000>5000Androgen
Dihydrotestosterone DHT; 5α-Androstanolone0.01 (<0.001–0.05)0.0059–0.17221–>500073–1688Androgen
Nandrolone 19-Nortestosterone; 19-NT0.010.2376553Androgen
Dehydroepiandrosterone DHEA; Prasterone0.038 (<0.001–0.04)0.019–0.07245–1053163–515Androgen
5-Androstenediol A5; Androstenediol6173.60.9Androgen
4-Androstenediol –0.50.62319Androgen
4-Androstenedione A4; Androstenedione<0.01<0.01>10000>10000Androgen
3α-Androstanediol 3α-Adiol0.070.326048Androgen
3β-Androstanediol 3β-Adiol3762Androgen
Androstanedione 5α-Androstanedione<0.01<0.01>10000>10000Androgen
Etiocholanedione 5β-Androstanedione<0.01<0.01>10000>10000Androgen
Methyltestosterone 17α-Methyltestosterone<0.0001 ? ? ?Androgen
Ethinyl-3α-androstanediol 17α-Ethynyl-3α-adiol4.0<0.07 ? ?Estrogen
Ethinyl-3β-androstanediol 17α-Ethynyl-3β-adiol505.6 ? ?Estrogen
Progesterone P4; 4-Pregnenedione<0.001–0.6<0.001–0.010 ? ?Progestogen
Norethisterone NET; 17α-Ethynyl-19-NT0.085 (0.0015–<0.1)0.1 (0.01–0.3)1521084Progestogen
Norethynodrel 5(10)-Norethisterone0.5 (0.3–0.7)<0.1–0.221453Progestogen
Tibolone 7α-Methylnorethynodrel0.5 (0.45–2.0)0.2–0.076 ? ?Progestogen
Δ4-Tibolone 7α-Methylnorethisterone0.069–<0.10.027–<0.1 ? ?Progestogen
3α-Hydroxytibolone –2.5 (1.06–5.0)0.6–0.8 ? ?Progestogen
3β-Hydroxytibolone –1.6 (0.75–1.9)0.070–0.1 ? ?Progestogen
Footnotes:a = (1) Binding affinity values are of the format "median (range)" (# (#–#)), "range" (#–#), or "value" (#) depending on the values available. The full sets of values within the ranges can be found in the Wiki code. (2) Binding affinities were determined via displacement studies in a variety of in-vitro systems with labeled estradiol and human ERα and ERβ proteins (except the ERβ values from Kuiper et al. (1997), which are rat ERβ). Sources: See template page.
Triphenylethylene. Triphenylethylene.svg
Triphenylethylene.

Estrogens closely related to the stilbestrols include paroxypropione (a metabolite of diethylstilbestrol) and the anise and fennel-derived compounds anol, dianol, anethole, dianethole, and photoanethole (from which the stilbestrol estrogens were actually originally derived). The triphenylethylene group of estrogenic drugs that includes triphenylethylene itself, estrobin, chlorotrianisene, broparestrol, ethamoxytriphetol, clomifene, tamoxifen, and more recently developed derivatives is also very closely related structurally to the stilbestrols.

Resveratrol is a stilbenoid with estrogenic properties that is not technically a stilbestrol derivative (it is 3,4',5-stilbenetriol). [6]

Occupational exposure

Occupational exposure to stilbestrol has resulted in gynaecomastia in workers. [7]

See also

References

  1. 1 2 3 Noller KL, Fish CR (July 1974). "Diethylstilbestrol usage: Its interesting past, important present, and questionable future". Med. Clin. North Am. 58 (4): 793–810. doi:10.1016/s0025-7125(16)32122-8. PMID   4276416.
  2. 1 2 VITAMINS AND HORMONES. Academic Press. 1 January 1945. pp.  233–. ISBN   978-0-08-086600-0.
  3. ↑ William John Edward Jessop (12 May 2014). Fearon's Introduction to Biochemistry. Elsevier. pp. 408–. ISBN   978-1-4831-9556-8.
  4. ↑ Actions and Uses of Drugs. Stanford University Press. pp. 234–. ISBN   978-0-8047-1505-8.
  5. ↑ Kuiper, George G. J. M.; Carlsson, Bo; Grandien, Kaj; Enmark, Eva; Häggblad, Johan; Nilsson, Stefan; Gustafsson, Jan-Åke (1997). "Comparison of the Ligand Binding Specificity and Transcript Tissue Distribution of Estrogen Receptors α and β". Endocrinology. 138 (3): 863–870. doi: 10.1210/endo.138.3.4979 . ISSN   0013-7227. PMID   9048584.
  6. ↑ Bhat KP, Lantvit D, Christov K, Mehta RG, Moon RC, Pezzuto JM; Lantvit; Christov; Mehta; Moon; Pezzuto (October 2001). "Estrogenic and antiestrogenic properties of resveratrol in mammary tumor models". Cancer Res. 61 (20): 7456–63. PMID   11606380.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ↑ Fitzsimons, P.M. (October 1944). "Gynaecomastia in Stilboestrol Workers". Br J Ind Med. 1 (4): 235–237. PMC   1035620 .
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