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Fitoterapia Jul 2020Sarcorusones A-D (1-4), four new androstane (C19-steroid) derivatives were characterized from Sarcococca ruscifolia along with five known compounds. Their structures...
Sarcorusones A-D (1-4), four new androstane (C19-steroid) derivatives were characterized from Sarcococca ruscifolia along with five known compounds. Their structures were elucidated on the basis of extensive MS and NMR spectroscopic analysis. All the new structures share common 14-hydroxyl and 17-ketone functional groups, and compounds 2-4 feature a seneciamide group connecting to C-3 position. The inhibitory activities of all the isolates against melanoma cell B16F10 and lung cancer cell H1299 were evaluated, and compounds 2, 3, 5, and 6 exhibited moderate cytotoxic activities against B16F10 and H1299 cell lines with IC values 2.7-8.0 μM.
Topics: Androstanes; Animals; Antineoplastic Agents, Phytogenic; Buxaceae; Cell Line, Tumor; China; Humans; Melanoma, Experimental; Mice; Molecular Structure; Phytochemicals
PubMed: 32380036
DOI: 10.1016/j.fitote.2020.104604 -
Molecules (Basel, Switzerland) Sep 2020The biotransformation of steroid compounds is a promising, environmentally friendly route to new pharmaceuticals and hormones. One of the reaction types common in the...
The biotransformation of steroid compounds is a promising, environmentally friendly route to new pharmaceuticals and hormones. One of the reaction types common in the metabolic fate of steroids is Baeyer-Villiger oxidation, which in the case of cyclic ketones, such as steroids, leads to lactones. Fungal enzymes catalyzing this reaction, Baeyer-Villiger monooxygenases (BVMOs), have been shown to possess broad substrate scope, selectivity, and catalytic performance competitive to chemical oxidation, being far more environmentally green. This study covers the biotransformation of a series of androstane steroids (epiandrosterone and androsterone) and androstene steroids (progesterone, pregnenolone, dehydroepiandrosterone, androstenedione, 19-OH-androstenedione, testosterone, and 19-nortestosterone) by the cultures of filamentous fungus AM110. The transformation was monitored by GC and the resulting products were identified on the basis of chromatographic and spectral data. The investigated fungus carries out effective Baeyer-Villiger oxidation of the substrates. Interestingly, introduction of the 19-OH group into androstenedione skeleton has significant inhibitory effect on the BVMO activity, as the 10-day transformation leaves half of the 19-OH-androstenedione unreacted. The metabolic fate of epiandrosterone and androsterone, the only 5α-saturated substrates among the investigated compounds, is more complicated. The transformation of these two substrates combined with time course monitoring revealed that each substrate is converted into three products, corresponding to oxidation at C-3 and C-17, with different time profiles and yields.
Topics: Androstanes; Androstenedione; Androsterone; Biotransformation; Chromatography, Gas; Mixed Function Oxygenases; Nandrolone; Oxidation-Reduction; Penicillium; Substrate Specificity
PubMed: 32942593
DOI: 10.3390/molecules25184226 -
Planta Medica Jun 2005Two new withanolides, cinerolide and 24,25-dihydrowithanolide S, together with the new androstane, cinedione, and the known withanolides, visconolide, physalactone,...
Two new withanolides, cinerolide and 24,25-dihydrowithanolide S, together with the new androstane, cinedione, and the known withanolides, visconolide, physalactone, withanolide S and 4beta-hydroxywithanolide E were isolated from the EtOAc extract of leaves, flowers and stems of Physalis cinerascens. The structures of these compounds were established by spectroscopic methods and that of cinerolide was confirmed by X-ray diffraction analysis.
Topics: Androstanes; Crystallography, X-Ray; Ergosterol; Flowers; Humans; Physalis; Phytotherapy; Plant Extracts; Plant Leaves; Plant Stems
PubMed: 15971127
DOI: 10.1055/s-2005-864157 -
Bioorganic & Medicinal Chemistry Nov 2015Biological investigation was conducted to study in vitro antiproliferative and pro-apoptotic potential of selected 17α-picolyl and 17(E)-picolinylidene androstane...
Biological investigation was conducted to study in vitro antiproliferative and pro-apoptotic potential of selected 17α-picolyl and 17(E)-picolinylidene androstane derivatives. The antiproliferative impact was examined on six human tumor cell lines, including two types of breast (MCF-7 and MDA-MB-231), prostate (PC3), cervical (HeLa), colon (HT 29) and lung cancer (A549), as well as one normal fetal lung fibroblasts cell line (MRC-5). All derivatives selectively decreased proliferation of estrogen receptor negative MDA-MB-231 breast cancer cells after 48 h and 72 h treatment and compounds showed time-dependent activity. We used this cell line to investigate cell cycle modulation and apoptotic cell death induction by flow cytometry, expression of apoptotic proteins by Western blot and apoptotic morphology by visual observation. Tested androstane derivatives affected the cell cycle distribution and induced apoptosis and necrosis. Compounds had different and specific mode of action, depending on derivative type and exposure time. Some compounds induced significant apoptosis measured by Annexin V test compared to reference compound formestane. Higher expression of pro-apoptotic BAX, downregulation of anti-apoptotic Bcl-2 and cleavage of PARP protein were confirmed in almost all treated samples, but the lack of caspase-3 activation suggested the induction of apoptosis in caspase-independent manner. More cells with apoptotic morphology were observed in samples after prolonged treatment. Structure-activity relationship analysis was performed to find correlations between the structure variations of investigated derivatives and observed biological effects. Results of this study showed that some of the investigated androstane derivatives have good biomedical potential and could be candidates for anticancer drug development.
Topics: Androstanes; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Caspase 3; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Female; HT29 Cells; HeLa Cells; Humans; Poly(ADP-ribose) Polymerases; Proto-Oncogene Proteins c-bcl-2; Structure-Activity Relationship; bcl-2-Associated X Protein
PubMed: 26494582
DOI: 10.1016/j.bmc.2015.10.015 -
Chemical & Pharmaceutical Bulletin May 2002Two androstane alkaloids were isolated from the musk of Moschus moschiferus. The structures were elucidated to be 3alpha-ureido-androst-4-en-17-one (1) and...
Two androstane alkaloids were isolated from the musk of Moschus moschiferus. The structures were elucidated to be 3alpha-ureido-androst-4-en-17-one (1) and 3alpha-ureido-androst-4-en-17beta-ol (2) by two-dimensional NMR analysis (HMQC, 1H-1H COSY, HMBC, and NOESY).
Topics: Alkaloids; Androstanes; Animals; Deer; Exocrine Glands; Fatty Acids, Monounsaturated; Magnetic Resonance Spectroscopy; Spectrometry, Mass, Fast Atom Bombardment; Spectrophotometry, Infrared
PubMed: 12036025
DOI: 10.1248/cpb.50.663 -
The Journal of Steroid Biochemistry and... Oct 2023Cancer remains a major health concern worldwide. The most frequently diagnosed types of cancer are caused by abnormal production or action of steroid hormones. In the...
Cancer remains a major health concern worldwide. The most frequently diagnosed types of cancer are caused by abnormal production or action of steroid hormones. In the present study, the synthesis and structural characterization of new heterocyclic androstane derivatives with D-homo lactone, 17α-(pyridine-2''-ylmethyl) or 17(E)-(pyridine-2''-ylmethylidene) moiety are presented. All compounds were evaluated for their anti-proliferative activity against HeLa cervical cancer cell line and non-cancerous kidney MDCK cells, where A-homo lactam compound 9A showed the greatest selectivity. Based on in vitro binding assays, N-formyl lactam compound 18 appeared to be the strong and isoform-selective ligand for ERα, while compound 9A displayed binding affinity for the GR-LBD, but also inhibited aldo-keto reductase 1C4 enzyme. Out of four selected compounds, methylpyrazolo derivative 13 showed potential for aromatase binding, while in silico studies provided insight into experimentally confirmed protein-ligand interactions.
Topics: Humans; Ligands; Androstanes; Steroids; Antineoplastic Agents; Lactams; Structure-Activity Relationship; Cell Proliferation; Molecular Structure; Drug Screening Assays, Antitumor; Cell Line, Tumor
PubMed: 37451557
DOI: 10.1016/j.jsbmb.2023.106362 -
Organic Letters Mar 2021The total synthesis of (+)-03219A, a rare Δ-pregnene isolated from the marine-derived sp. SCSIO 03219, is described that is based on a series of transformations that...
The total synthesis of (+)-03219A, a rare Δ-pregnene isolated from the marine-derived sp. SCSIO 03219, is described that is based on a series of transformations that enable progression from epichlorohydrin to an -estrane, then conversion to a -androstane, and finally establishment of the natural product target. Key to the success of these studies was implementation of two rearrangement processes to formally invert the quaternary center at C13 and establish the C10 quaternary center.
Topics: Androstanes; Estranes; Molecular Structure; Pregnenes; Streptomyces
PubMed: 33635666
DOI: 10.1021/acs.orglett.1c00382 -
Nature Oct 1998The orphan receptor CAR-beta binds DNA as a heterodimer with the retinoid-X receptor and activates gene transcription in a constitutive manner. Here we show that, in...
The orphan receptor CAR-beta binds DNA as a heterodimer with the retinoid-X receptor and activates gene transcription in a constitutive manner. Here we show that, in contrast to the classical nuclear receptors, the constitutive activity of CAR-beta results from a ligand-independent recruitment of transcriptional co-activators. While searching for potential ligands of CAR-beta, we found that the steroids androstanol and androstenol inhibit the constitutive activity of CAR-beta. This effect is stereospecific: only 3alpha-hydroxy, 5alpha-reduced androstanes are active. These androstanes do not interfere with heterodimerization or DNA binding of CAR-beta; instead, they promote co-activator release from the ligand-binding domain. These androstane ligands are examples of naturally occurring inverse agonists that reverse transcriptional activation by nuclear receptors. CAR-beta (constitutive androstane receptor-beta), therefore, defines an unanticipated steroidal signalling pathway that functions in a manner opposite to that of the conventional nuclear receptor pathways.
Topics: Androstanes; Androstanols; Animals; Binding Sites; COS Cells; Constitutive Androstane Receptor; Ligands; Receptors, Cytoplasmic and Nuclear; Recombinant Fusion Proteins; Saccharomyces cerevisiae; Stereoisomerism; Trans-Activators; Transcription Factors; Transfection
PubMed: 9783588
DOI: 10.1038/26996 -
Steroids Feb 2017The newly synthesized (α/β)-diastereomers of 6-(N-methyl-N-phenyl)aminomethylandrost-4-ene-3,17-dione (5) and...
The newly synthesized (α/β)-diastereomers of 6-(N-methyl-N-phenyl)aminomethylandrost-4-ene-3,17-dione (5) and 6-(N-methyl-N-phenyl)aminomethylandrost-4-en-17β-ol-3-one (6) were firstly investigated as substrates for the whole cells of Nocardioides simplex VKM Ac-2033D in comparison with their unsubstituted analogs, - androst-4-ene-3,17-dione (1) and androst-4-en-17β-ol-3-one (2). 1(2)-Dehydroderivatives were identified as the major bioconversion products from all the substrates tested. When using the mixtures of (α/β)-stereoisomers of 5 and 6 as the substrates, only β-stereoisomers of the corresponding 1,4-diene-steroids were formed. Along with 1(2)-dehydrogenation, N. simplex VKM Ac-2033D promoted oxidation of the hydroxyl group at C-17 position of 6: both 6(α) and 6(β) were transformed to the corresponding 17-keto derivatives. No steroid core destruction was observed during the conversion of the 6-substituted androstanes 5 and 6, while it was significant when 1 or 2 was used as the substrate. The results suggested high potentials of N. simplex VKM Ac-2033D for the generation of novel 1(2)-dehydroanalogs.
Topics: Actinobacteria; Androstanes; Magnetic Resonance Spectroscopy; Molecular Structure; Stereoisomerism; Steroids
PubMed: 27864019
DOI: 10.1016/j.steroids.2016.11.001 -
Endocrinology Dec 1960
Topics: Androgens; Androstanes; Hydrocarbons
PubMed: 13749674
DOI: 10.1210/endo-67-6-887