107012-17-9Relevant academic research and scientific papers
Antiestrogenically active 1,1,2-tris(4-hydroxyphenyl)alkenes without basic side chain: Synthesis and biological activity
Lubczyk, Veronika,Bachmann, Helmut,Gust, Ronald
, p. 1484 - 1491 (2007/10/03)
C2-Alkyl substituted derivatives of the 1,1,2-tris(4-hydroxyphenyl)ethene 3a (alkyl = Me (3b), Et (3c), Prop (3d), But (3e)) were synthesized by reaction of 1,2-bis(4-methoxyphenyl)ethanone with the appropriate alkyl halide, followed by a Grignard reaction with 4-methoxyphenylmagnesium bromide, dehydration with phosphoric acid or hydrobromic acid, and ether cleavage with BBr3. The compounds were tested for estrogen receptor (ER) binding affinity in a competition experiment with radio labeled estradiol ([3H]-E2) and for gene activation on the ER-positive MCF-7-2a cell line. All compounds showed high receptor binding affinity (RBA-value: 3b (52. 1%) > 3a (45.5%) > 3c (29.6%) > 3d (4.03%) > 3e (0.95%)). The tests on hormone dependent MCF-7-2a breast cancer cells, stably transfected with the plasmid EREwtcluc, revealed that all 1,1,2-tris(4-hydroxyphenyl)ethenes antagonized the effect of 1 nM estradiol (E2). The compounds 3b (IC50 = 15 nM) and 3c (IC50 = 10 nM) were equal in their effects to 4-hydroxytamoxifen (4OHT) (IC50 = 7 nM). Agonistic effects were low. Only 3a and 3b activated the luciferase expression (relative activation at 1 μM: 3a 60%; 3b 35%). Despite their highly antagonistic potency, the 1,1,2-tris(4-hydroxyphenyl)ethenes showed only low cytotoxic properties on the hormone sensitive MCF-7 cell line.
1,1,2-Triphenylbut-1-enes: Relationship between Structure, Estradiol Receptor Affinity, and Mammary Tumor Inhibiting Properties
Schneider, Martin R.,Angerer, Erwin von,Schoenenberger, Helmut,Michel, Ralf Th.,Fortmeyer, H. P.
, p. 1070 - 1077 (2007/10/02)
1,1,2-Triphenylbut-1-enes, which are substituted with acetoxy groups on one, two, or three aromatic rings in the para and/or meta positions, were synthesized.The identity of the occurring E and Z isomers were established by 1H NMR spectroscopy.A study on structure-activity relationships was carried out with regard to estradiol receptor affinity and to inhibiting effects on the growth of a postmenopausal human mammary carcinoma implanted in nude mice.The para-substituted compounds generally exhibited a higher receptor affinity and a better antitumor activity than the corresponding meta-substituted ones.The E isomers were superior to the respective Z isomers in those two properties.The tumor-inhibiting effect of the mono-and disubstituted compounds was better than that of the trisubstituted ones.Except for the trisubstituted compounds, they all showed a good correlation between estradiol receptor affinity and antitumor activity.One of the compounds was also tested on the 9,10-dimethylbenzanthracene-induced, hormone-dependent mammary carcinoma of the Spraque-Dawley rat, and the results corresponded to those obtained in the xenograft tumor.
