[Effects of gomisin J and analogous lignan compounds in schisandra fruits on isolated smooth muscles].
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Animals↗
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Results for “Polycyclic Compounds”
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Hyrtiosal, a PTP1B inhibitor from the marine sponge Hyrtios erectus, shows extensive cellular effects on PI3K/AKT activation, glucose transport, and TGFbeta/Smad2 signaling.
Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling, and PTP1B inhibitors have been seen as promising therapeutic agents against obesity and type 2 diabetes. Here we report that the marine natural product hyrtiosal, from the marine sponge Hyrtios erectus, has been discovered to act as a PTP1B inhibitor and to show extensive cellular effects on PI3K/AKT activation, glucose transport, and TGFbeta/Smad2 signaling. This inhibitor wad able to inhibit PTP1B activity in dose-dependent fashion, with an IC(50) value of 42 microM in a noncompetitive inhibition mode. Further study with an IN Cell Analyzer 1000 cellular fluorescence imaging instrument showed that hyrtiosal displayed potent activity in abolishing the retardation of AKT membrane translocation caused by PTP1B overexpression in CHO cells. Moreover, it was found that this newly identified PTP1B inhibitor could dramatically enhance the membrane translocation of the key glucose transporter Glut4 in PTP1B-overexpressed CHO cells. Additionally, in view of our recent finding that PTP1B was able to modulate insulin-mediated inhibition of Smad2 activation, hyrtiosal was also tested for its capabilities in the regulation of Smad2 activity through the PI3K/AKT pathway. The results showed that hyrtiosal could effectively facilitate insulin inhibition of Smad2 activation. Our current study is expected to supply new clues for the discovery of PTP1B inhibitors from marine natural products, while the newly identified PTP1B inhibitor hyrtiosal might serve as a potential lead compound for further research.
Animals↗
Aspects of schizandrin metabolism in vitro and in vivo.
The metabolic transformation of schizandrin, isolated from the kernel of Schizandra chinensis Bill, was studied in vitro with a phenobarbital induced rat liver microsomal fraction containing the NADPH generating system. The major metabolites were isolated by preparative HPLC and identified as 7,8-dihydroxy-schizandrin, 7,8-dihydroxy-2-demethyl-schizandrin, and 7,8-dihydroxy-3-demethyl-schizandrin by UV, NMR and MS spectral analysis. The 7,8-dihydroxy-schizandrin was confirmed further by comparison with spectral and chromatographic behavior of the authentic compound. The metabolic biotransformation of schizandrin in vivo was also determined.
Animals↗
Metabolism of nitropolycyclic aromatic hydrocarbons by human intestinal microflora.
Anaerobic bacterial suspensions from human and rat feces and intestinal contents, and pure cultures of anaerobic bacteria metabolized 1-nitropyrene and 6-nitrobenzo[a]pyrene to 1-aminopyrene and 6-aminobenzo[a]pyrene, respectively. The metabolites were isolated by reversed-phase high performance liquid chromatography and identified by comparison of their chromatographic and mass spectral properties with those of authentic compounds. The results suggest that anaerobic intestinal bacteria could play a significant role in the metabolism of potentially carcinogenic nitropolycyclic aromatic hydrocarbons.
Anaerobiosis↗
Reversion of bioluminescent bacteria (Mutatox) to their luminescent state upon exposure to organic compounds, munitions, and metal salts.
Mutatox is a new genotoxicity bioassay which uses as the endpoint the bioluminescence produced on reversion of a dark strain of the marine bacterium Vibrio fischeri +/- S9. Reversion can occur by several mechanisms, including base substitution, frame-shift, SOS induction, and DNA intercalation. For screening, Mutatox provides many advantages over the Salmonella typhimurium (Ames) assay: it requires minimal sterility, employs a shorter incubation period, and does not require culture maintenance. Eighteen organic chemicals (phenol, polynuclear aromatic hydrocarbons, nitrotoluenes, others), Na3PO4, and 4 genotoxic metals (Cu2+, Ni2+, As3+, Cd2+) were tested. Most of the organic compounds positive in S. typhimurium assays were positive in Mutatox. None of the metals was genotoxic in V. fischeri, possibly due to poor uptake from the saline medium.
Luminescent Measurements↗
Comparative effects of a highly specific protein kinase C inhibitor, calphostin C and calmodulin inhibitors on angiotensin-stimulated aldosterone secretion.
We have examined the relative roles of the calcium-calmodulin system and protein kinase C in angiotensin-mediated aldosterone secretion. We used a highly specific protein kinase C inhibitor, calphostin C and two well-accepted calmodulin inhibitors, W-7 and calmidazolium. Although both types of inhibitors affected angiotensin-induced aldosterone secretion, as judged by the inhibitory doses of these compounds, angiotensin-evoked aldosterone secretion was more sensitive to calmodulin inhibition than protein kinase C inhibition. Manipulation of OFFracellular calcium by dantrolene and thapsigargin also modified aldosterone secretion significantly.
Aldosterone↗
Characterization and determination of organic compounds in the mutagenic XAD-2 extracts of drinking water.
Amberlite XAD-2 extracts, which exhibit mutagenicity in the Ames assays, of drinking water sampled each month during the period from April 1988 to March 1989 were studied in order to characterize and determine the organic pollutants. The major organic pollutants were phthalate ester plasticizers such as dibutyl and di(2-ethylhexyl) phthalate. Several polynuclear aromatic hydrocarbons (PAHs) and the organocholorine pesticide oxadiazon were also identified to be present at low concentrations. The XAD-extractable and chromatographable organic pollutants were found to be composed of PAHs with a mean concentration of 0.136 micrograms/l(ca. 10% of the total amount of organic compounds detected), phthalates with a mean value of 0.405 micrograms/l(ca. 30%) and other compounds with a mean value of 0.845 micrograms/l(ca. 60%). The concentrations and compositions of these organic pollutants were correlated with the effective rainfall content of the river and with the water temperature.
Ion Exchange Resins↗
Helical structure of tercyclopropanedimethanol in solution.
Oligocyclopropanes with repetitive stereochemistry occur in two unusual natural products with interesting bioactivity. X-ray crystal structures are available for these compounds but with partially contradicting results. Because the 1H and 13C NMR spectra of oligocyclopropanes are far from trivial to be assigned even at highest magnetic fields, we have prepared a specifically deuterated sample and have applied high field NMR spectroscopy and DFT calculations to determine its conformation. The helix with equal handedness shown in the stereopicture was found for tercyclopropanedimethanol. A dihedral angle of around +40 degrees is the best representation of the experimental data and characterizes, therefore, the dominating helical conformation of tercyclopropanedimethanol with a single repetitive (+)-gauche interunit dihedral angle. This is in full agreement with the crystal structure of the all syn,trans-quinquecyclopropanedimethanol with an R configuration at the termini that also adopted an all (+)-gauche conformation. However, the crystal structure of the title compound and the solution structure are different.
Crystallography, X-Ray↗
BENZO(A)PYRENE AND OTHER POLYNUCLEAR HYDROCARBONS IN CHARCOAL-BROILED MEAT.
The possible production of carcinogenic polynuclear hydrocarbons in the charcoal broiling of food has been investigated. Fifteen steaks were cooked and the polynuclear compounds were extracted, separated by chromatography, and identified spectrometrically. Many polynuclear hydrocarbons were identified, but no nitrogen heterocyclic compounds were detected. The carcinogen benzo(a)pyrene was present in the average amount of 8 micrograms per kilogram of steak.
Anthracenes↗
Effects of environmental chemicals on the metabolism of drugs, carcinogens, and normal body constituents in man.
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17-Ketosteroids↗
The recognition of higher-order G-quadruplex by chiral cyclic-helicene molecules.
The G-quadruplex structures represent a new class of molecular targets for DNA-interactive compounds that might be useful for targeting telomeres. Here we describe a study on the structure-based design of cyclic helicenes displaying chiral and steric selection in binding to higher-order G-quadruplexes. We propose a new ligand-binding site for G-quadruplex-binding compounds. These results provide proof of concept for small molecule inhibitors of telomerase associated with higher-order G-quadruplex structures.
Binding Sites↗
Sensitive method for the determination of nitrated polycyclic aromatic hydrocarbons in the human diet.
The presence of nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) as contaminants in foods is nowadays a legitimate cause of concern, as they are reported to be strong direct-acting mutagens and carcinogens that may pose a risk to human health. Nevertheless, their concentrations in foods are in the ultra-trace region. In this study, we present a very sensitive analytical method for the determination of this compound class in complex food matrices. Special emphasis was put on sample extraction and clean up. Recoveries of 75% could be obtained for 1- and 2-nitronaphthalene; for all other compounds investigated the recoveries were >/=94%. The determination of the compounds was performed by gas chromatography-mass spectrometry. The results show that the use of negative chemical ionization (NCI) increases the sensitivity by one order of magnitude in comparison to electron impact ionization (EI) (limits of detection 0.07-0.25 micro g kg(-1) for EI and 0.01-0.02 micro g kg(-1) for NCI). The influence of the sample matrix on the sensitivity of the method is demonstrated with extracts of a sample from a duplicate diet study. Due to the lack of a certified reference material the suitability of the method is demonstrated with pumpkin seed oil that was spiked with nitro-PAHs at two different concentration levels.
Chromatography, Gel↗
Topographic recognition of cyclic hydrocarbons and related compounds by receptors for androgens, estrogens, and glucocorticoids.
The structural requirements for the interaction of about 80 cyclic hydrocarbons and related compounds with the androgen receptor of rat ventral prostate, the estrogen receptor of human breast tumor MCF-7 cells, and the glucocorticoid receptor of rat liver were examined by comparing their abilities to compete with radioactive hormones for binding to the respective receptors. The results indicate that the receptor-binding affinity of a compound is dependent on its electronic configuration and geometrical similarity to a portion of a natural steroid hormone which can be recognized by local ligand-binding sites in the receptor. For the estrogen receptor, beta-phenols are more active than the corresponding alpha-phenols, whereas nonphenolic compounds are totally inactive. For androgen and glucocorticoid receptors, alpha-phenols are more active than beta-phenols. The androgen receptor can interact stereospecifically with nonoxygenated and nonalkylated cyclic hydrocarbons, such as 10,11-dihydro-5H-dibenzo[a,d] cycloheptene or 9,10-dihydrophenanthrene, which can, in vivo, inhibit the androgen-dependent growth of the male accessory reproductive organs. The affinities of naphthalene, anthracene, phenanthrene, biphenyl, and adamantane toward glucocorticoid and androgen receptors can be enhanced by acetylation or ethanolization of these ligands. Our results also indicate that, while the hormonal action of a steroid may be dependent on the interaction of a functional group on the hormone with a specific group on the receptor, the presence of such a group may not be required for the antagonistic activity of a compound that can physically block hormone binding to the receptor. Thus, many small molecules that were hitherto considered to be biologically inert may interact with steroid receptors specifically and affect hormonal activities in vivo.
Animals↗
State of research: environmental pathways and food chain transfer.
Data on the chemistry of biologically active components of petroleum, synthetic fuel oils, certain metal elements and pesticides provide valuable generic information needed for predicting the long-term fate of buried waste constituents and their likelihood of entering food chains. Components of such complex mixtures partition between solid and solution phases, influencing their mobility, volatility and susceptibility to microbial transformation. Estimating health hazards from indirect exposures to organic chemicals involves an ecosystem's approach to understanding the unique behavior of complex mixtures. Metabolism by microbial organisms fundamentally alters these complex mixtures as they move through food chains. Pathway modeling of organic chemicals must consider the nature and magnitude of food chain transfers to predict biological risk where metabolites may become more toxic than the parent compound. To obtain predictions, major areas are identified where data acquisition is essential to extend our radiological modeling experience to the field of organic chemical contamination.
Air Pollutants↗
[A new bibenzyl derivative from Bletilla striata].
AIM: To study the chemical constituents of Bletilla striata. METHODS: Various column chromatographies with silica gel and Sephadex LH-20 were employed for the isolation and purification. The structures of the compounds were elucidated on the basis of spectral analyses and chemical methods. RESULTS: Three compounds were isolated from the roots of Bletilla striata (Thunb.) Reichb. f. and identified as 5-hydroxy-4-(p-hydroxybenzyl)-3'-3-dimethoxybibenzyl (I), schizandrin (II), 4,4'-dimethoxy-(1,1'-biphenanthrene)-2,2',7,7'-tetrol (III). CONCLUSION: Compound I is a new bibenzyl derivative and II was isolated from this plant for the first time.
Bibenzyls↗
Relationship between "aromatic hydrocarbon responsiveness" and the survival times in mice treated with various drugs and environmental compounds.
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9,10-Dimethyl-1,2-benzanthracene↗
Synthesis and activity of a C-8 keto pleuromutilin derivative.
A C-8 keto pleuromutilin derivative has been synthesized from the biotransformation product 8-hydroxy mutilin. A key step in the process was the selective oxidation at C-8 of 8-hydroxy mutilin using tetrapropylammonium perruthenate. The presence of the C-8 keto group precipitated interesting intramolecular chemistry to afford a compound (10) with a novel pleuromutilin-derived ring system.
Biotransformation↗
[Protective effects of schisanhenol, salvianolic acid A and SY-L on oxidative stress induced injuries of cerebral cells and their mechanisms].
Oxidative stress may play an important role in neuronal degenerative diseases such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. These disorders make the elderly not being able to live normally and move freely. So it is necessary to find effective antioxidants to prevent or cure the aged persons from diseases related to neuronal degeneration. Schisanhenol (Sal) and salvianolic acid A (Sal A) are known antioxidants which were isolated from Chinese herbs respectively. SY-L is a totally synthetic new compound. The results showed that Sal, Sal A and SY-L significantly protect cerebral cells from the injuries induced by oxidative stress.
Alzheimer Disease↗