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Biotransformation of oral contraceptive ethynodiol diacetate with microbial and plant cell cultures.Chemistry Central Journal Sep 2012Biotransformation by using microbial and plant cell cultures has been applied effectively for the production of fine chemicals on large scale. Inspired by the wealth of...
BACKGROUND
Biotransformation by using microbial and plant cell cultures has been applied effectively for the production of fine chemicals on large scale. Inspired by the wealth of literature available on the biotransformation of steroids, we decided to investigate the biotransformation of ethynodiol diacetate (1) by using plant and microbial cultures.
RESULTS
The biotransformation of ethynodiol diacetate (1) with Cunninghamella elegans and plant cell suspension cultures of Ocimum basilicum and Azadirachta indica is being reported here for the first time. Biotransformation of 1 with Cunninghamella elegans yielded three new hydroxylated compounds, characterized as 17α-ethynylestr-4-en-3β,17β-diacetoxy-6α-ol (2), 17α-ethynylestr-4-en-3β,17β-diacetoxy-6β-ol (3), and 17α-ethynylestr-4-en-3β,17β-diacetoxy-10β-ol (4) and a known metabolite, 17α-ethynyl-17β-acetoxyestr-4-en-3-one (5). The biotransformation of 1 with Ocimum basilicum included hydrolysis of the ester group, oxidation of alcohol into ketone, and rearrangement of the hydroxyl group. Thus four major known metabolites were characterized as 17α-ethynyl-17β-acetoxyestr-4-en-3-one (5), 17α-ethynyl-17β-hydroxyestr-4-en-3-one (6), 17α-ethynyl-3 β-hydroxy-17β-acetoxyestr-4-ene (7) and 17α-ethynyl-5α,17β-dihydroxyestr-3-ene (8). Biotransformation of 1 with Azadirachta indica culture yielded compounds 5 and 6. Spectroscopic data of compound 8 is being reported for the first time. Structure of compound 6 was unambiguously deduced through single-crystal x-ray diffraction studies.
CONCLUSION
Biotransformation of an oral contraceptive, ethynodiol diacetate (1), by using microbial and plant cell cultures provides an efficient route to the synthesis of a library of new steroids with potential contraceptive properties. These methods can be employed in the production of such compounds with high stereoselectivity.
PubMed: 23021311
DOI: 10.1186/1752-153X-6-109 -
Scientific African Sep 2021The current crisis of the COVID-19 pandemic around the world has been devastating as many lives have been lost to the novel SARS CoV-2 virus. Thus, there is an urgent...
The current crisis of the COVID-19 pandemic around the world has been devastating as many lives have been lost to the novel SARS CoV-2 virus. Thus, there is an urgent need for the right therapeutic drug to curb the disease. However, there is time constraint in drug development, hence the need for drug repurposing approach, a relatively fast and less expensive alternative. In this study, 1,100 Food and Drug Administration (FDA) approved drugs were obtained from DrugBank and trimmed to 791 ligands based on illicitness, withdrawal from the market, being chemical agents rather than drugs, being investigational drugs and having molecular weight greater than 500 (Kg/mol). The ligands were docked against six drug targets of the novel SARS CoV-2 - 3-chymotrypsin-like protease (3CLpro), Angiotensin-converting enzyme (ACE2), ADP ribose phosphatase of NSP3 (NSP3), NSP9 RNA binding protein (NSP9), RNA dependent RNA polymerase (RdRp) and Replicase Polyprotein 1a (RP1a). UCSF Chimera, PyRx and Discovery Studio, were used to prepare the proteins, dock the ligands and visualize the complexes, respectively. Remdesivir, Lopinavir and Hydroxychloroquine were used as reference drugs. Pharmacokinetic properties of the ligands were obtained using AdmetSAR. The binding energies of the standard drugs ranged from -5.4 to -8.7 kcal/mol while over 400 of the ligands screened showed binding energy lower than -5.4 kcal/mol. Out of the 791 number of compounds docked, 10, 91, 132, 92, 54 and 96 compounds showed lower binding energies than all the controls against 3CLPro, ACE2, NSP3, NSP9, RP1a and RdRp, respectively. Ligands that bound all target proteins, and showed the lowest binding energies with good ADMET properties and particularly showed the lowest binding against ACE2 are ethynodiol diacetate (-15.6 kcal/mol), methylnaltrexone (-15.5 kcal/mol), ketazolam (-14.5 kcal/mol) and naloxone (-13.6 kcal/mol). Further investigations are recommended for ethynodiol diacetate, methylnaltrexone, ketazolam and naloxone through preclinical and clinical studies to ascertain their effectiveness.
PubMed: 34308004
DOI: 10.1016/j.sciaf.2021.e00845 -
Fertility and Sterility Nov 1974
Topics: Adolescent; Adult; Alopecia; Body Weight; Endometrium; Ethynodiol Diacetate; Female; Headache; Humans; Lactation; Leukorrhea; Luteinizing Hormone; Menstruation; Muscle Contraction; Nervous System Diseases; Ovulation; Pregnancy; Time Factors; Uterus; Vomiting
PubMed: 4426405
DOI: 10.1016/s0015-0282(16)40750-8 -
British Medical Journal Aug 1969
Topics: Adult; Dysmenorrhea; Ethynodiol Diacetate; Female; Humans; Lactation Disorders; Mestranol; Pregnancy
PubMed: 5816595
DOI: 10.1136/bmj.3.5669.529-b -
Journal of Clinical Pathology Mar 1979
Topics: Abnormalities, Drug-Induced; Adrenal Glands; Contraceptives, Oral, Combined; Ethynodiol Diacetate; Female; Humans; Male; Mestranol; Pregnancy
PubMed: 429599
DOI: 10.1136/jcp.32.3.305 -
British Medical Journal Mar 1968
Review
Topics: Chlormadinone Acetate; Contraceptives, Oral; Ethynodiol Diacetate; Humans; Lynestrenol; Norethindrone; Norethynodrel; Progestins
PubMed: 4171189
DOI: No ID Found -
Cleveland Clinic Journal of Medicine May 1990Spironolactone (Aldactone), 100 mg to 200 mg daily, has antiandrogenic effects that may enhance treatment of androgen-excess syndromes, particularly severe hirsutism....
Spironolactone (Aldactone), 100 mg to 200 mg daily, has antiandrogenic effects that may enhance treatment of androgen-excess syndromes, particularly severe hirsutism. Combination therapy with an oral contraceptive or with dexamethasone appears to have a beneficial effect. Side effects are transient. The drug should be avoided during pregnancy and in women who have a family history of breast cancer, although there is no proven association between spironolactone and breast malignancy.
Topics: Contraceptives, Oral; Dexamethasone; Drug Therapy, Combination; Female; Hirsutism; Humans; Spironolactone
PubMed: 2357784
DOI: 10.3949/ccjm.57.3.285 -
Fertility and Sterility Apr 1983The effect synthetic progestins found in current oral contraceptives may exert on respiratory function has not been thoroughly investigated. This study monitored...
The effect synthetic progestins found in current oral contraceptives may exert on respiratory function has not been thoroughly investigated. This study monitored potential changes in respiratory parameters 3 and 6 months subsequent to beginning administration. Static and timed spirometric maneuvers showed significant increases in only tidal volume (P = 0.01). Ventilatory response to treadmill exercise monitored the oxygen uptake, CO2 elimination (VCO2), minute ventilation (VE), and respiratory exchange ratio at each of four workloads. An analysis of the covariance (ANCOVA) for the slopes revealed no significant variation between test periods. The ANCOVA for the means showed increases in VE and VCO2. These results suggest a stimulatory role for synthetic progestins, although ventilatory performance in response to moderate exercise does not appear compromised.
Topics: Adult; Contraceptives, Oral; Contraceptives, Oral, Synthetic; Female; Humans; Oxygen Consumption; Physical Exertion; Progesterone Congeners; Pulmonary Gas Exchange; Respiration; Rest; Vital Capacity
PubMed: 6832407
DOI: 10.1016/s0015-0282(16)46943-8 -
Fertility and Sterility 1968
Topics: Analysis of Variance; Animals; Biological Assay; Contraceptives, Oral; Estrogens; Ethynodiol Diacetate; Female; Fertility; Hypothalamo-Hypophyseal System; Mice; Norethindrone; Norethynodrel; Organ Size; Ovary; Uterus
PubMed: 5647620
DOI: 10.1016/s0015-0282(16)36671-7 -
Fertility and Sterility Aug 1976A 3-hour oral glucose tolerance test was conducted in "normal" women before and after 12 months of contraceptive treatment with daily 0.25-mg ethynodiol diacetate...
A 3-hour oral glucose tolerance test was conducted in "normal" women before and after 12 months of contraceptive treatment with daily 0.25-mg ethynodiol diacetate tablets. There was no significant change in the subjects' weight between the two tests. All but the 3-hour individual group glucose values were significantly elevated at the 1-year test, and 16.7% of the tolerance curves became "borderline abnormal". The group plasma insulin values for the 0.5-, 1-, and 2-hour samples during the 1-year test were also significantly elevated. There was a significant decrease in the group fasting triglyceride levels but no change in the fasting cholesterol levels. These data suggest that some of the 19-norprogestogens may adversely affect carbohydrate metabolism.
Topics: Adult; Blood Glucose; Carbohydrates; Cholesterol; Ethynodiol Diacetate; Female; Humans; Insulin; Lipids; Triglycerides
PubMed: 955132
DOI: 10.1016/s0015-0282(16)42009-1