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Acta Obstetricia Et Gynecologica... 1994Danazol, a weakly androgenic, heterocyclic compound with anabolic properties, is used primarily in the treatment of endometriosis and other gynecological complaints.... (Review)
Review
Danazol, a weakly androgenic, heterocyclic compound with anabolic properties, is used primarily in the treatment of endometriosis and other gynecological complaints. Early reports indicated that the drug had little effect on plasma lipid (cholesterol and triglyceride) levels but recently concern has been expressed over more subtle changes reported in plasma lipid and lipoprotein metabolism after danazol treatment. Therapy produces a rapid reduction in high density lipoprotein (HDL) cholesterol (particularly in the putatively cardioprotective HDL2 subfraction) coupled with a rise in the pro-atherogenic low density lipoprotein (LDL). These apparently unwanted actions are balanced against a possibly beneficial reduction in the atherogenic lipoprotein(a) fraction. The mechanism of these changes induced by danazol is unknown but probably relates to effects on hepatic lipase, LDL receptor and lecithin cholesterol acyl transferase activity. While it is prudent to recognize the potential detriment that may follow these perturbations, concern is only warranted where therapy is prolonged (> 12 months) or given to subjects with a high background risk of ischemic heart disease.
Topics: Cholesterol; Danazol; Endometriosis; Female; Humans; Lipid Metabolism; Lipoproteins
PubMed: 8209670
DOI: No ID Found -
Chemical Biology & Drug Design Jun 2017Danazol, the established clinical drug, has given promising therapeutic results in a series of clinical trials with breast cancer patients. Danazol shares structural...
Danazol, the established clinical drug, has given promising therapeutic results in a series of clinical trials with breast cancer patients. Danazol shares structural similarities with several known PKC agonists and fits well into the C1 domain. Danazol binds to the C1b domain of PKC with K of 5.64 ± 1.27 μm. MD simulation studies further support that the PKC-danazol molecular model is stable and showing minimum distortion to the structure during the simulation period. Immunofluorescence and Western blotting studies indicate that MDAMB-231 cells stimulated with danazol exhibit translocation of PKCα to the plasma membrane. Cells stimulated with danazol causes appearance of several phosphorylated proteins in lysate and plasma membrane. In addition, danazol affects carcinogenic molecule (PMA)-induced intracellular signaling in cancer cells. It halted the cancer cells in the G1 phase of the cell cycle and reduced the viability of ER and triple-negative breast cancer cells with an IC of 31 ± 2.63 and 65 ± 4.27 μg/ml, respectively. DNA fragmentation and flow cytometry experiments revealed that the cell death follows the apoptotic pathway. It affects mitochondrial membrane potentials and releases cytochrome-C from mitochondria to induce downstream apoptosis in breast cancer cells. Hence, the current study may help clinicians to re-design their treatment strategy to optimize therapeutic potentials of the molecule.
Topics: Apoptosis; Breast Neoplasms; Cell Cycle; Cell Survival; Danazol; Drug Delivery Systems; Female; Humans; Immunoblotting; Inhibitory Concentration 50; MCF-7 Cells; Membrane Potential, Mitochondrial; Phosphorylation; Protein Kinase C; Signal Transduction
PubMed: 27933735
DOI: 10.1111/cbdd.12921 -
Journal of Minimally Invasive Gynecology 2006
Topics: Contraceptives, Oral, Synthetic; Danazol; Endometriosis; Estrogen Antagonists; Female; Fertility Agents, Female; Humans; Medroxyprogesterone; Nafarelin; Pelvic Pain
PubMed: 17097573
DOI: 10.1016/j.jmig.2006.06.026 -
Cancer Chemotherapy and Pharmacology 1983Pre-menopausal (14) and post-menopausal (55) patients with advanced breast cancer were treated with danazol (Danol) for periods ranging between 3 days and 30 months. Of... (Clinical Trial)
Clinical Trial
Pre-menopausal (14) and post-menopausal (55) patients with advanced breast cancer were treated with danazol (Danol) for periods ranging between 3 days and 30 months. Of these, 10 patients (14.9%) responded to treatment for 3-19 months (mean 10 months); a further six patients (9%) showed stabilisation of disease; 45 patients showed clear progression of disease following treatment; and eight patients were unassessable. Side-effects occurred in 17 of 69 patients (25%) and necessitated a reduction in therapy in eight cases. It is concluded that danazol is moderately well tolerated and is an effective agent in patients with advanced breast cancer, but the response rate is inferior to that of other agents in current use, such as tamoxifen or aminoglutethimide.
Topics: Adult; Aged; Breast Neoplasms; Clinical Trials as Topic; Danazol; Female; Humans; Menopause; Middle Aged; Neoplasm Metastasis; Pregnadienes; Prognosis
PubMed: 6345017
DOI: 10.1007/BF00255761 -
Natural Product Letters Apr 2002Danazol (17beta-hydroxy-17alpha-pregna-2,4-dien-20-yno-[2,3-d] isoxazole) (1) on fermentation with Fusarium lini, Aspergillus niger, and Cephalosporium aphidicola...
Danazol (17beta-hydroxy-17alpha-pregna-2,4-dien-20-yno-[2,3-d] isoxazole) (1) on fermentation with Fusarium lini, Aspergillus niger, and Cephalosporium aphidicola yielded 17beta-hydroxy-2-(hydroxymethyl)-17-alpha-pregn-4-en-20-yn-3-one (2) and 17beta-hydroxy-2-(hydroxymethyl)-17 alpha-pregna-1,4-dien-20-yn-3-one (3), while the fermentation of 1 with Bacillus cerus yielded compound 2 only.
Topics: Acremonium; Aspergillus niger; Bacillus cereus; Biotransformation; Danazol; Fermentation; Fusarium; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular
PubMed: 11990425
DOI: 10.1080/10575630290019994 -
Cancer Chemotherapy and Pharmacology 1981
Topics: Danazol; Humans; Pregnadienes; Progesterone Congeners; Steroids
PubMed: 7273264
DOI: 10.1007/BF00253018 -
AAPS PharmSciTech May 2007This study explored the potential of beta-cyclodextrin to improve the aqueous solubility and dissolution of danazol, investigated a simple and less expensive method for...
This study explored the potential of beta-cyclodextrin to improve the aqueous solubility and dissolution of danazol, investigated a simple and less expensive method for preparation of a danazol-beta-cyclodextrin binary system, and explored the potential application of a danazol-beta-cyclodextrin binary system as a single-dose emergency contraceptive. Phase solubility analysis indicated formation of a first-order soluble complex with stability constant 972.03 M(-1), while Job's plot affirmed 1:1 stoichiometry. The hyperchromic shift in the UV-Vis spectrum of danazol in the presence of beta-cyclodextrin indicated solubilization capability of beta-cyclodextrin for danazol. The extrinsic Cotton effect with a negative peak at 280.7 nm confirmed the inclusion of danazol in the asymmetric locus of beta-cyclodextrin. (1)H-nuclear magnetic resonance analysis suggested that the protons of the steroidal skeleton of danazol display favorable interactions with the beta-cyclodextrin cavity. The danazol-beta-cyclodextrin binary system was prepared by kneading, solution, freeze-drying, and milling methods. The extent of the enhancement of dissolution rate was found to be dependent on the preparation method. Dissolution studies showed a similar relative dissolution rate (2.85) of the danazol-beta-cyclodextrin binary system prepared by the freeze-drying and milling (in the presence of 13% moisture) methods. In a mouse model, the danazol-beta-cyclodextrin binary system at 51.2 mg/kg (equivalent to a 400-mg human dose) showed 100% inhibition of implantation when given postcoitally. Moreover, the danazol-beta-cyclodextrin binary system is safe up to 2000 mg/kg in the mouse (15.52 g/70 kg human) as a single oral dose. Thus, the danazol-beta-cyclodextrin binary system could serve as a new therapeutic application: an oral emergency contraceptive at a physiologically acceptable single dose.
Topics: Animals; Circular Dichroism; Contraceptives, Oral; Contraceptives, Postcoital; Danazol; Embryo Implantation; Female; Magnetic Resonance Spectroscopy; Male; Mice; Progesterone; Solubility; Spectrophotometry, Ultraviolet; beta-Cyclodextrins
PubMed: 17622113
DOI: 10.1208/pt0802035 -
The Journal of Rheumatology Oct 1995To determine the efficacy of danazol for refractory autoimmune thrombocytopenia or Evans' syndrome complicating systemic lupus erythematosus (SLE). (Clinical Trial)
Clinical Trial
OBJECTIVE
To determine the efficacy of danazol for refractory autoimmune thrombocytopenia or Evans' syndrome complicating systemic lupus erythematosus (SLE).
METHODS
We studied 16 consecutive patients with SLE and corticosteroid refractory autoimmune thrombocytopenia; 3 patients had coexisting autoimmune hemolysis (Evans' syndrome). Five patients had undergone splenectomy. Danazol was commenced at 200 mg/day, and increased stepwise (maximum 1200 mg/day) until benefit or toxicity was observed. After remission the danazol dose was gradually reduced to 200-400 mg/day.
RESULTS
All 16 patients achieved a complete remission (platelet count >100 x 10(9)/l, hematocrit >39%) 2 months after starting danazol (range 6 weeks-8 months). Remission persisted during continued danazol therapy (mean followup 18.2 months, range 2-49 months). One patient with Evans' syndrome required discontinuation of danazol because of jaundice and biopsy proven minimal hepatic necrosis: hemolysis recurred after discontinuation of danazol.
CONCLUSION
Danazol is effective for the treatment of autoimmune thrombocytopenia or Evans' syndrome complicating SLE irrespective of splenectomy status. Longer followup will be needed to determine whether the remission persists after withdrawal of danazol.
Topics: Adult; Anemia, Hemolytic; Autoimmune Diseases; Danazol; Female; Humans; Lupus Erythematosus, Systemic; Middle Aged; Prospective Studies; Remission Induction; Splenectomy; Syndrome; Thrombocytopenia
PubMed: 8991983
DOI: No ID Found -
Annals of Internal Medicine Jan 1980
Topics: Adult; Creatine Kinase; Danazol; Female; Humans; Hypothyroidism; Pregnadienes; Thyroxine; Thyroxine-Binding Proteins
PubMed: 6766050
DOI: 10.7326/0003-4819-92-1-133_2 -
British Journal of Haematology Sep 1993
Topics: Blood Cell Count; Blood Platelets; Danazol; Humans; Myelodysplastic Syndromes
PubMed: 8251401
DOI: 10.1111/j.1365-2141.1993.tb08681.x