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Sample records for mestranol

  1. Parallel Solid-Phase Synthesis Using a New Diethylsilylacetylenic Linker and Leading to Mestranol Derivatives with Potent Antiproliferative Activities on Multiple Cancer Cell Lines.

    Science.gov (United States)

    Dutour, Raphael; Maltais, Rene; Perreault, Martin; Roy, Jenny; Poirier, Donald

    2018-03-07

    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. Using solid-phase strategy involving five steps, we quickly synthesized a series of RM-581 analogs using the recently-developed diethylsilyl acetylenic 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). 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). Easily synthesized in good yields by both solid-phase organic synthesis and classic solution-phase chemistry, this promising candidate could be used as an antiproliferative agent on a variety of cancers, notably pancreatic and ovarian cancers, both having very bad prognoses. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. A survey of 17α-ethinylestradiol and mestranol residues in Hawkesbury River, Australia, using a highly specific enzyme-linked immunosorbent assay (ELISA) demonstrates the levels of potential biological significance.

    Science.gov (United States)

    Uraipong, Chatchaporn; Allan, Robin D; Li, Chunhua; Kennedy, Ivan R; Wong, Victor; Lee, Nanju Alice

    2017-10-01

    This study reports on the potential status of 17α-ethinylestradiol (EE2) and mestranol (MeEE2) residues in aquatic environments in New South Wales (NSW), Australia, based on the analysis by a specific ELISA we developed. Polyclonal antibodies were raised against the EE2 hapten with a linker attached at the C3-position to direct the antibody binding towards the ring D of EE2/MeEE2. Using this approach, an ELISA highly specific to EE2 and MeEE2 was successfully developed, showing less than 3.1% cross-reactivity (% CR) with other major steroidal sex hormones and their derivatives. The assay performed with the limit of detection (LOD) of 0.04 ± 0.01µg/L for both EE2 and MeEE2, and the limit of quantitation (LOQ) of 0.05 ± 0.01ng/L when it was coupled with the SM2-Biobeads solid phase extraction. Prior to conducting the survey study, it was validated against the gas chromatography-mass spectrophotometry (GC-MS) method, which showed high correlation with R 2 of 0.934. Fresh surface water samples collected at different sites along Hawkesbury River in New South Wales (NSW) were analyzed for the EE2/ MeEE2 residues using the developed ELISA. The EE2/MeEE2 levels were found to range between 4.1 and 8.3ng/L in Emigrant Creek, NSW, where the primary activity was macadamia plantation, and higher levels between 15 and 29ng/L in South Creek, NSW, Greater Western Sydney at sites upstream and downstream of the municipal sewage treatment plants. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Long-term experience with Enovid among clinic patients: results after 2 and one-half to 6 years of individual patient use.

    Science.gov (United States)

    Sturtevant, R P

    1970-08-01

    64 women clients of Planned Parenthood of Evansville (Indiana) used Enovid (5 mg norethynodrel and .075 mg mestranol, combined) for 2 1/2 to 6 years. A "25-Month Club" card and free pills were given to encourage continuation in the study, and 33 women (52%) remained until study termination. The group ranged in age from 18-40 years, mean 27 years, and in parity 0 to 12, mean 4. No pregnancies, cancer of reproductive organs or thromboembolism occurred. Side effects, recorded by interview according to a standard form, included: cervicitis 48%, vaginal discharge 42%; dysmenorrhea 61% pretreatment, 42% improved, 11% new symptoms; breast complaints 33%; 2-15 lb weight gain 19%. 12% reported no side effects, although the author commented that the 25-Month Club policy might have discouraged reporting of side effects.

  4. An enquiry on appropriate selection of polymers for preparation of polymeric nanosorbents and nanofiltration/ultrafiltration membranes for hormone micropollutants removal from water effluents.

    Science.gov (United States)

    Khansary, Milad Asgarpour; Mellat, Mostafa; Saadat, Seyed Hassan; Fasihi-Ramandi, Mahdi; Kamali, Mehdi; Taheri, Ramezan Ali

    2017-02-01

    To analyze polymeric nanosorbents and nanofiltration/ultrafiltration membranes for hormone micropollutants removal from water effluents, here an in-through investigation on the suitability and compatibility of various polymers has been carried out. For this work, estradiol, estrone, testosterone, progesterone, estriol, mestranol, and ethinylestradiol were considered. A total number of 452 polymers were analyzed and initially screened using Hansen solubility parameters. The identified good pairs of hormones and polymers then were examined to obtain the equilibrium capacity of hormones removal from water effluents using a modified Flory-Huggins model. A distribution coefficient was defined as the ratio of hormones in water effluent phase and polymer phase. For removal of mestranol, estradiol and ethinylestradiol, no compatible polymer was identified based on initial screening of collected database. Three compatible polymers were identified for estriol. For progesterone, a wide variety of polymers was identified as good matching of polar, dispersion and hydrogen forces contributions can be observed for these pairs. For estrone, only two polymers can be proposed due to the mismatch observed between polar, dispersion and hydrogen forces contributions of other polymers and this hormone. The phase calculations showed that not all the identified good pairs could be used for practical separation applications. The domain of applicability of each good pair was investigated and potential polymers for practical micropollutants removal together with their removal capacity were represented in terms of phase envelops. The theoretical approach follows fundamental chemical thermodynamic equations and then can be simply applied for any system of interest. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Trace analysis of selected hormones and sterols in river sediments by liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.

    Science.gov (United States)

    Matić, Ivana; Grujić, Svetlana; Jauković, Zorica; Laušević, Mila

    2014-10-17

    In this paper, development and optimization of new LC-MS method for determination of twenty selected hormones, human/animal and plant sterols in river sediments were described. Sediment samples were prepared using ultrasonic extraction and clean up with silica gel/anhydrous sodium sulphate cartridge. Extracts were analyzed by liquid chromatography-linear ion trap-tandem mass spectrometry, with atmospheric pressure chemical ionization. The optimized extraction parameters were extraction solvent (methanol), weight of the sediment (2 g) and time of ultrasonic extraction (3× 10 min). Successful chromatographic separation of hormones (estriol and estrone, 17α- and 17β-estradiol) and four human/animal sterols (epicoprostanol, coprostanol, α-cholestanol and β-cholestanol) that have identical fragmentation reactions was achieved. The developed and optimized method provided high recoveries (73-118%), low limits of detection (0.8-18 ng g(-1)) and quantification (2.5-60 ng g(-1)) with the RSDs generally lower than 20%. Applicability of the developed method was confirmed by analysis of six river sediment samples. A widespread occurrence of human/animal and plant sterols was found. The only detected hormone was mestranol in just one sediment sample. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Estrogenic potential of the Venice, Italy, lagoon waters.

    Science.gov (United States)

    Pojana, Giulio; Bonfà, Angela; Busetti, Francesco; Collarin, Anna; Marcomini, Antonio

    2004-08-01

    The exposure of the Venice lagoon (Italy) to endocrine-disrupting compounds (EDCs) from different sources was investigated. Spatial and time distribution of EDC concentrations were determined in four sampling sessions (December 2001-May 2002) by solid phase extraction followed by high-performance liquid chromatography separation coupled with mass spectrometry detection via electrospray interface (SPE-HPLC-ESI-MS), which allowed identification of natural (estradiol, estrone) and synthetic estrogenic compounds, both steroidal (ethinylestradiol, mestranol) and nonsteroidal (benzophenone, bisphenol-A, nonylphenol, nonylphenol monoethoxylate carboxylate). No significant differences in the EDC distribution were observed between stations located near selected sources (raw sewage from the historical center of Venice, treated municipal and industrial effluents from sewage treatment plants, and areas undergoing the inflow of rivers). While synthetic nonsteroidal analytes were recorded in the 1 to 1040 ng/L range (average concentration: 34 ng/L), steroidal EDC (estradiol, ethinylestradiol) concentrations were lower (1-125 ng/L; average concentration: 8 ng/L). The estrogenic activity of lagoon waters was estimated in terms of estradiol equivalent concentration (EEQ) by applying the estradiol equivalency factors (EEFs). Steroidal EDCs (estradiol, ethinylestradiol) contributed >97% to the total potential estrogenicity of the waters, which accounted for 4 to 172 ng/L (average: 25 ng/L), as total EEQs. These levels are likely to pose adverse effects on the Venice lagoon aquatic organisms.

  7. New low-dose, extended-cycle pills with levonorgestrel and ethinyl estradiol: an evolutionary step in birth control.

    Science.gov (United States)

    Nelson, Anita

    2010-08-09

    To review milestones in development of oral contraceptive pills since their introduction in the US 50 years ago in order to better understand how a new formulation with low-dose estrogen in an extended-cycle pattern fits into the evolution of birth control pills. This is a review of trends in the development of various birth controls pills and includes data from phase III clinical trials for this new formulation. The first birth control pill was a very high-dose monophasic formulation with the prodrug estrogen mestranol and a first-generation progestin. Over the decades, the doses of hormones have been markedly reduced, and a new estrogen and several different progestins were developed and used in different dosing patterns. The final element to undergo change was the 7-day pill-free interval. Many of these same changes have been made in the development of extended-cycle pill formulation. The newest extended-cycle oral contraceptive formulation with 84 active pills, each containing 20 μg ethinyl estradiol and 100 μg levonorgestrel, represents an important evolution in birth control that incorporates lower doses of estrogen (to reduce side effects and possibly reduce risk of thrombosis), fewer scheduled bleeding episodes (to meet women's desires for fewer and shorter menses) and the use of low-dose estrogen in place of placebo pills (to reduce the number of days of unscheduled spotting and bleeding). Hopefully, this unique formation will motivate women to be more successful contraceptors.

  8. [Effect of oral contraceptives on the psyche and on sexuality].

    Science.gov (United States)

    Nahrendorf, G; Carol, W; Klinger, G

    1978-01-01

    The problem of whether or not oral contraceptives affect the psychic function of the female is still controversal. The purpose of the present investigation was to study the occurrence of psychic and sexual effects in women taking either Ovosiston (mestranol 0,08 mg + chlormadinone acetate 2, 0 mg) or Non-Ovlon (ethinylestradiol 0,05 mg + norethisterone acetate 1,0 mg). 186 somatically healthy women were subject to two interviews, immediately before the start of therapy and six months after it. Most of the patients recorded distinctly alterations of their mood, their initiative, their elemental desires such as appetite, sleep, need of warmth, and their sexual behaviour. 73 of them noted a change in their emotional pattern, which was positive in 34 and negative in 39 cases. 99 women reported changes in their elemental desires. 136 patients exhibited alterations of their sexual behaviour, which were assessed as an improvement or impairment in 108 and 28 cases, respectively. There is a statistically significant correlation between the impairment of sexual function and the incidence of other untoward side effects. On the other hand, negative suggestion by poor experience of other women on by the influence of mass media seems to play a minor role in producing changes of sexual behaviour. There is, however, a clearcut relationship between negative suggestion and the incidence of unfavourable emotional alterations. The findings are discussed with reference to their clinical significance.

  9. Ozone oxidation of oestrogenic active substances in wastewater and drinking water.

    Science.gov (United States)

    Baig, S; Hansmann, G; Paolini, B

    2008-01-01

    Ozone oxidation is proven to be an effective solution for the degradation of selected oestrogenic active substances detected in secondary wastewaters such as beta-oestradiol, oestrone, oestriol, 17-alpha-ethinyloestradiol, mestranol, daidzeine, beta-sitosterol, bisphenol A, norethisterone, 4-tert-octylphenol and 4-iso-nonylphenol, up to their limit of detection. The matrix-effect of wastewater was investigated performing ozone experiments under batch mode and continuous mode using drinking water and a wastewater issued from a local plant both spiked with the non-detected substances. The results obtained indicate that the wastewater matrix greatly affects the kinetics of ozone reaction with these substances but does not really change the related reactivity scale. The ozone dose corresponding to the full conversion of target EDCs consequently increases as their oxidation takes place competing with reactions of background pollutants represented by the COD and DOC content. However, a usual dose close to 12 mg/L was found sufficient to provide high degradation yields for all substances studied while 35% of COD was removed. This is a contribution to the numerous current works focused on technologies able to improve the quality of water discharged from wastewater treatment plants, both considering conventional parameters and emerging contaminants. IWA Publishing 2008.

  10. Oral contraceptives and the prothrombin time.

    Science.gov (United States)

    Pangrazzi, J; Roncaglioni, M C; Donati, M B

    1980-02-02

    Dr. De Teresa and others reported that mean prothrombin time ratio of 12 patients on long-term anticoagulation with warfarin was significantly higher when they were also taking oral contraceptives (OCs). A study of prothrombin complex activity was recently conducted in female rats treated with an estrogen-progestogen combination (lynestrenol 5 mg; mestranol 0.3 mg/kg body weight) which resulted in a 100% infertility in this species. After 1 treatment for only 1 estral cycle, OC-treated rats had a significantly longer Normotest clotting time (37.7+ or-0.5 sec) than control rats (31.0+or-0.4); the difference was even more notable after 10 cycles. Although this finding has not been reported in women on OCs, it may be that the estrogen-induced "lability" of the prothrombin complex occurs in humans only in special conditions, such as anticoagulation. Alternatively, liver dysfunction occurring among women on OCs may be responsible for reduced metabolism of warfarin, contributing to the effectiveness of the anticoagulation. Further pharmacology studies should be done to clarify the interaction between OCs and oral anticoagulants.

  11. [Hyperplastic changes and oral contraceptives in Anglo-Saxon countries].

    Science.gov (United States)

    Markuszewski, C

    1978-09-18

    One of the major problems being researched and studied by the World Health Organization is the incidence of harmful side effects in users of steroid contraceptives. A literature search indicates that Anglo-Saxon countries report alarming hyperplastic changes, particularly in the liver, blood clots, hyperlipidemia leading to high blood pressure, porphyria, atypical leiomyomas and cervical hyperplasia. Currently attention is being focused on the relationship between steroid contraceptives and breast cancer. Fazala and Paffenbarger in their study of 1770 women found such benign changes as fibroadenoma, mastopathia fibrosa cystica and papilloma intraductale. In women who had used oral contraceptives for 2-4 yrs, malignancies were 1.9% to 2.5% more frequent than in non-users; in 6 yrs of use, 11 times greater than in non-users. Estrogens, particularly mestranol has been recognized as being harmful to the liver. Length of usage is a definite factor. Beginning with 1960, relatively frequent occurrences of hepotoma in young women on the pill were noted. Caught at an early stage, peliosis hepatis can be reversed if the patient discontinues the use of contraceptives. In some cases, even after a long interval of 6 months to 10 yrs, the disease continued to develop. Liver cell adenoma in the U. S. occurs 1/500,00 to 1/1,000,000. After 5 to 7 yrs of using oral contraceptives, the chance of developing liver cell adenoma is 5 times greater; after 10 yrs of use, 35 times greater. Hepatomas rupture in 43.4% of cases when the patient had been on a contraceptive, while in only 22.2% in cases of non-users. The literature which the author investigated did not establish a clear proof that the hyperplastic changes discussed were due exclusively to usage of oral contraceptives.

  12. Chemical approach to solvent removal during nanoencapsulation: its application to preparation of PLGA nanoparticles with non-halogenated solvent

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Youngme [Ewha Womans University, College of Pharmacy (Korea, Republic of); Sah, Eric [University of Notre Dame, College of Science (United States); Sah, Hongkee, E-mail: hsah@ewha.ac.kr [Ewha Womans University, College of Pharmacy (Korea, Republic of)

    2015-11-15

    The objective of this study was to develop a new oil-in-water emulsion-based nanoencapsulation method for the preparation of PLGA nanoparticles using a non-halogenated solvent. PLGA (60–150 mg) was dissolved in 3 ml of methyl propionate, which was vortexed with 4 ml of a 0.5–4 % polyvinyl alcohol solution. This premix was sonicated for 2 min, added into 30 ml of the aqueous polyvinyl alcohol solution, and reacted with 3 ml of 10 N NaOH. Solvent removal was achieved by the alkaline hydrolysis of methyl propionate dissolved in an aqueous phase into water-soluble methanol and sodium propionate. It was a simple but effective technique to quickly harden nanoemulsion droplets into nanoparticles. The appearing PLGA nanoparticles were recovered by ultracentrifugation and/or dialysis, lyophilized with trehalose, and redispersed by water. This nanoencapsulation technique permitted a control of their mean diameters over 151.7 ± 3.8 to 440.2 ± 22.2 nm at mild processing conditions. When the aqueous polyvinyl alcohol concentration was set at ≥1 %, nanoparticles showed uniform distributions with polydispersity indices below 0.1. There were no significant changes in their mean diameters and size distribution patterns before and after lyophilization. When mestranol was encapsulated into nanoparticles, the drug was completely nanoencapsulated: depending on experimental conditions, their encapsulation efficiencies were determined to be 99.4 ± 7.2 to 105.8 ± 6.3 %. This simple, facile nanoencapsulation technique might have versatile applications for the preparation of polymeric nanoparticulate dosage forms.Graphical AbstractSchematic illustration of an innovative chemical approach to solvent removal during nanoencapsulation. Methyl propionate present in the aqueous continuous phase reacts with sodium hydroxide, thereby producing methanol and sodium propionate. Its alkaline hydrolysis allows the continuous extraction of the solvent out of nanoemulsion

  13. Chemical approach to solvent removal during nanoencapsulation: its application to preparation of PLGA nanoparticles with non-halogenated solvent

    International Nuclear Information System (INIS)

    Lee, Youngme; Sah, Eric; Sah, Hongkee

    2015-01-01

    The objective of this study was to develop a new oil-in-water emulsion-based nanoencapsulation method for the preparation of PLGA nanoparticles using a non-halogenated solvent. PLGA (60–150 mg) was dissolved in 3 ml of methyl propionate, which was vortexed with 4 ml of a 0.5–4 % polyvinyl alcohol solution. This premix was sonicated for 2 min, added into 30 ml of the aqueous polyvinyl alcohol solution, and reacted with 3 ml of 10 N NaOH. Solvent removal was achieved by the alkaline hydrolysis of methyl propionate dissolved in an aqueous phase into water-soluble methanol and sodium propionate. It was a simple but effective technique to quickly harden nanoemulsion droplets into nanoparticles. The appearing PLGA nanoparticles were recovered by ultracentrifugation and/or dialysis, lyophilized with trehalose, and redispersed by water. This nanoencapsulation technique permitted a control of their mean diameters over 151.7 ± 3.8 to 440.2 ± 22.2 nm at mild processing conditions. When the aqueous polyvinyl alcohol concentration was set at ≥1 %, nanoparticles showed uniform distributions with polydispersity indices below 0.1. There were no significant changes in their mean diameters and size distribution patterns before and after lyophilization. When mestranol was encapsulated into nanoparticles, the drug was completely nanoencapsulated: depending on experimental conditions, their encapsulation efficiencies were determined to be 99.4 ± 7.2 to 105.8 ± 6.3 %. This simple, facile nanoencapsulation technique might have versatile applications for the preparation of polymeric nanoparticulate dosage forms.Graphical AbstractSchematic illustration of an innovative chemical approach to solvent removal during nanoencapsulation. Methyl propionate present in the aqueous continuous phase reacts with sodium hydroxide, thereby producing methanol and sodium propionate. Its alkaline hydrolysis allows the continuous extraction of the solvent out of nanoemulsion