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Chemical & Pharmaceutical Bulletin Aug 2005The microbial transformation of an oral contraceptive, mestranol (1) by Cunninghamella elegans yielded two hydroxylated metabolites, 6beta-hydroxymestranol (2) and...
The microbial transformation of an oral contraceptive, mestranol (1) by Cunninghamella elegans yielded two hydroxylated metabolites, 6beta-hydroxymestranol (2) and 6beta,12beta-dihydroxymestranol (3). Metabolite 3 was found to be a new compound. These metabolites were structurally characterized on the basis of spectroscopic techniques.
Topics: Biotransformation; Cunninghamella; Magnetic Resonance Spectroscopy; Mestranol; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Ultraviolet
PubMed: 16079537
DOI: 10.1248/cpb.53.1011 -
Anti-cancer Agents in Medicinal... 2018RM-133 belongs to a new family of aminosteroid derivatives demonstrating interesting anticancer properties, as confirmed in vivo in four mouse cancer xenograft models....
Parallel Solid-Phase Synthesis using a New Diethylsilylacetylenic Linker and Leading to Mestranol Derivatives with Potent Antiproliferative Activities on Multiple Cancer Cell Lines.
BACKGROUND
RM-133 belongs to a new family of aminosteroid derivatives demonstrating interesting anticancer properties, as confirmed in vivo in four mouse cancer xenograft models. However, the metabolic stability of RM-133 needs to be improved. After investigation, the replacement of its androstane scaffold by a more stable estrane scaffold led to the development of the mestranol derivative RM-581.
METHODS
Using solid-phase strategy involving five steps, we quickly synthesized a series of RM-581 analogs using the recently-developed diethylsilylacetylenic linker. To establish structure-activity relationships, we then investigated their antiproliferative potency on a panel of cancer cell lines from various cancers (breast, prostate, ovarian and pancreatic).
RESULTS
Some of the mestranol derivatives have shown in vitro anticancer activities that are close to, or better than, those observed for RM-581. Compound 23, a mestranol derivative having a ((3,5-dimethylbenzoyl)- L-prolyl)piperazine side chain at position C2, was found to be active as an antiproliferative agent (IC50 = 0.38 ± 0.34 to 3.17 ± 0.10 µM) and to be twice as active as RM-581 on LNCaP, PC-3, MCF-7, PANC-1 and OVCAR-3 cancer cells (IC50 = 0.56 ± 0.30, 0.89 ± 0.63, 1.36 ± 0.31, 2.47 ± 0.91 and 3.17 ± 0.10 µM, respectively).
CONCLUSION
Easily synthesized in good yields by both solid-phase organic synthesis and classic solution-phase chemistry, promising compound 23 could be used as an antiproliferative agent on a variety of cancers, notably pancreatic and ovarian cancers, both having very bad prognoses.
Topics: Acetylene; Antineoplastic Agents; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Mestranol; Molecular Conformation; Solid-Phase Synthesis Techniques; Structure-Activity Relationship; Tumor Cells, Cultured
PubMed: 29521249
DOI: 10.2174/1871520618666180307130158 -
Casopis Lekaru Ceskych Jul 1972
Topics: Contraceptives, Oral; Evaluation Studies as Topic; Female; Humans; Mestranol; Ovulation; Pregnancy; Progestins
PubMed: 5079918
DOI: No ID Found -
American Journal of Obstetrics and... Dec 1968
Topics: Adult; Cervix Mucus; Contraceptives, Oral; Female; Humans; Menstruation; Mestranol; Norethindrone; Viscosity
PubMed: 5724391
DOI: 10.1016/0002-9378(68)90467-5 -
Steroids Dec 1975A mixture of 2-3H and 4-14C-mestranol was administered orally to five women and 2-3H-mestranol alone to one woman. Reactions involving position 2 were extensive as...
A mixture of 2-3H and 4-14C-mestranol was administered orally to five women and 2-3H-mestranol alone to one woman. Reactions involving position 2 were extensive as judged by liberation of 3H into body water (14-45% of the dose). 17alpha-Ethynylestradiol, 2-hydroxy-17alpha-ethynylestradiol, 2-methoxy-17alpha-ethynylestradiol, 2-hydroxy-17alpha-ethynylestradiol 3-methyl ether and 16geta-hydroxy-17alpha-ethynylestradiol were measured in the "glucuronide" and pH1 fractions and mestranol, D-homoestrone-17a and D-homoestradiol-17abeta were also measured in the "glucuronide" fraction frum the urine to two of the women by reverse isotope dilution. Radioactive 2-methoxyestradiol accounted for less than 0.011% of the 14C dose in the "glucuronide" fraction of one of the women, consistent with the extent of de-ethynylation previously reported (Steroids, 25, 343 (1975).
Topics: Adult; Body Height; Body Water; Body Weight; Carbon Radioisotopes; Female; Glucuronates; Humans; Mestranol; Norethindrone; Tritium
PubMed: 1216258
DOI: 10.1016/0039-128x(75)90104-x -
JAMA Jun 1969
Topics: Contraceptives, Oral; Female; Humans; Menstruation; Mestranol; Norethynodrel; Schizophrenia; Suicide Prevention
PubMed: 5818838
DOI: 10.1001/jama.1969.03160100098025 -
Cervical mucorrhea and spinnbarkeit in patients taking norethindrone plus mestranol (Norinyl 1-mg.).Fertility and Sterility 1968
Clinical Trial
Topics: Cervix Mucus; Clinical Trials as Topic; Drug Synergism; Female; Humans; Infertility, Female; Menstruation; Mestranol; Microscopy, Phase-Contrast; Norethindrone; Ovulation
PubMed: 4869631
DOI: 10.1016/s0015-0282(16)36669-9 -
Steroids May 2008Preparative chemical methods for the synthesis of 10 degradation or photodecomposition products of mestranol and ethinyl estradiol (EE) are described. The synthesized...
Preparative chemical methods for the synthesis of 10 degradation or photodecomposition products of mestranol and ethinyl estradiol (EE) are described. The synthesized compounds are useful as reference materials and standards for pharmaceutical analysis of mestranol and EE as bulk chemical or in formulated product. New synthetic methods were presented and the known synthetic procedures were improved. Detailed structural characterization of the degradation or photodecomposition products of mestranol and EE and related compounds was reported.
Topics: Estrogens; Ethinyl Estradiol; Mestranol
PubMed: 18255111
DOI: 10.1016/j.steroids.2007.12.024 -
Obstetrics and Gynecology Apr 1966
Topics: Adolescent; Adult; Aged; Drug Synergism; Female; Humans; Mestranol; Middle Aged; Norethindrone; Uterine Hemorrhage
PubMed: 5907368
DOI: 10.1097/00006250-196604000-00005 -
American Journal of Obstetrics and... Jul 1990Careful studies in an adequate sample of subjects show a very marked degree of variability in the pharmacokinetics of ethinyl estradiol--specifically, in parameters such... (Review)
Review
Careful studies in an adequate sample of subjects show a very marked degree of variability in the pharmacokinetics of ethinyl estradiol--specifically, in parameters such as area under the curve, half-life, and time to peak. This variability is seen in differences between different populations, as well as from one individual to another. These studies also show variability in area under the curve and other parameters in the same person from time to time. Such differences may equal or exceed the differences between low dose (35 micrograms) and high-dose (50 micrograms) formulations. The levels of plasma ethinyl estradiol produced by a 50 micrograms dose of mestranol are similar to those from 35 micrograms of ethinyl estradiol. Thus a high-dose pill may be no higher than a low-dose pill if the nature of the estrogen is not kept in mind. Qualitative differences in the oxidative metabolites of estrogens may be of significance with respect to oncogenic potential.
Topics: Biological Availability; Dose-Response Relationship, Drug; Ethinyl Estradiol; Female; Humans; Mestranol
PubMed: 2196804
DOI: 10.1016/0002-9378(90)90575-r