ABSTRACT
The steroidal enzyme cytochrome P45017alpha catalyzes the conversion of progesterone and pregnenolone into androgens, androstenedione and dehydroepiandrosterone, respectively, the direct precursors of estrogens and testosterone. Dihydrotestosterone is the principal active androgen in the prostate, testosterone is also an active stimulant of the growth of prostatic cancer tissue. Inhibition of this enzyme as a mechanism for inhibiting androgen biosynthesis could be a worthwhile therapeutic strategy for the treatment of PCA. In this paper, four categories of steroidal inhibitors of cytochrome P45017alpha will be reviewed, a diverse range of steroidal inhibitors had been synthesized and shown to be potent inhibitors of P45017alpha.
Subject(s)
Animals , Humans , Male , Androstenedione , Androstenes , Androstenols , Chemistry , Pharmacology , Antineoplastic Agents , Chemistry , Pharmacology , Dehydroepiandrosterone , Dihydrotestosterone , Metabolism , Enzyme Inhibitors , Chemistry , Pharmacology , Molecular Structure , Pregnenolone , Metabolism , Progesterone , Metabolism , Prostatic Neoplasms , Pathology , Steroid 17-alpha-Hydroxylase , TestosteroneABSTRACT
In order to improve transformation efficiency of dehydroepiandrosterone (DHEA) into 3beta,7alpha,15alpha-trihydroxy-5-androsten-17-one (7alpha,15alpha-diOH-DHEA) by Gibberella intermedia CA3-1, we investigated the strains breeding and their conversion process optimization. G. intermedia CA3-1 strains were treated with 0.12 mg/mL 1-methyl-3-nitro-1-nitroso-guanidin (NTG) for 30 min and chosen by 350 micromol/L minimum inhibitory concentration ketoconazole resistance marker. The high production strain named M-10 with a good genetic stability was selected and the product molar yield achieved to 70.2%, which was 20% higher than that of original strain. Under the improved conversion process with the DHEA concentration of 5 g/L, the product molar yield of the mutant M-10 reached 75.6%, which was improved by 31.3% than that of original strain.
Subject(s)
Androstenols , Metabolism , Biotransformation , Dehydroepiandrosterone , Metabolism , Gibberella , Metabolism , Industrial MicrobiologyABSTRACT
Prostate cancer is the most common non-cutaneous neoplasm in the male population worldwide. It is typically diagnosed in its early stages, and the disease exhibits a relatively indolent course in most patients. Despite the curability of localized disease with prostatectomy and radiation therapy, some patients develop metastatic disease and die. Although androgen deprivation is present in the majority of patients with metastatic prostate cancer, a state of androgen resistance eventually develops. Castration-resistant prostate cancer, defined when there is progression of disease despite low levels of testosterone, requires specialized care, and improved communication between medical and urologic oncologists has been identified as a key component in delivering effective therapy. Despite being considered a chemoresistant tumor in the past, the use of a prostate-specific antigen has paved the way for a new generation of trials for castration-resistant prostate cancer. Docetaxel is a life-prolonging chemotherapy that has been established as the standard first-line agent in two phase III clinical trials. Cabazitaxel, a novel taxane with activity in cancer models resistant to paclitaxel and docetaxel, is the only agent that has been compared to a chemotherapy control in a phase III clinical trial as a second-line therapy; it was found to prolong the overall survival of patients with castration-resistant prostate cancer previously treated with docetaxel when compared to mitoxantrone. Other agents used in this setting include abiraterone and sipuleucel-T, and novel therapies are continually being investigated in an attempt to improve the outcome for patients with castration-resistant prostate cancer.
Subject(s)
Humans , Male , Androgen Antagonists/therapeutic use , Antineoplastic Agents/therapeutic use , Orchiectomy , Prostatic Neoplasms/drug therapy , Androstenols/therapeutic use , Clinical Trials as Topic , Disease Progression , Evidence-Based Medicine , Prostatic Neoplasms/surgery , Taxoids/therapeutic use , Tissue Extracts/therapeutic useABSTRACT
<p><b>AIM</b>To study the impurity of the drug testosterone.</p><p><b>METHODS</b>Chromatography methods were used to separate the chemical constituents. Their structures were determined by NMR and MS spectral analysis.</p><p><b>RESULTS</b>Two new epimers were isolated from the mother liquid of the drug.</p><p><b>CONCLUSION</b>These new epimers were identified as 3alpha-ethoxyandrost-4-en-17beta-ol, 3beta-ethoxyandrost-4-en-17beta-ol.</p>
Subject(s)
Androstenols , Chemistry , Drug Contamination , Molecular Conformation , Molecular Structure , Stereoisomerism , Testosterone , ChemistryABSTRACT
Subcutaneous administration of RMI 12,936 at a dose level of 2 mg/rat on day 5 of unilaterally pregnant rat having trauma-induced decidual cell reaction (DCR) in the contralateral uterine horn, suppresses DCR, induces resorption of implanted embryos and leads to decrease in the plasma level of progesterone. Progesterone replacement (D 5-8) in this situation reverses DCR suppressive effect of RMI 12,936 but fails to prevent resorption of implanted embryos. It is concluded that possibly the drug simultaneously exerts embryotoxic as well as luteolytic effects, but these effects are independent.