Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Polycyclic Compounds”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 955 records · Page 53Linked to original sources
PubMed1990

Synthesis and pharmacological evaluation of a series of dibenzo[a,d]cycloalkenimines as N-methyl-D-aspartate antagonists.

A series of 73 dibenzo[a,d]cycloalkenimines were synthesized and evaluated for their ability to displace (+)-10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]-(+)-10) from its specific binding site on rat cortical membranes. A number of the more active compounds (Ki ranging from 0.006 to 0.21 microM) were evaluated for N-methyl-D-aspartate (NMDA) antagonist activity in the rat cortical slice (Kb ranging from 0.08 to 0.9 microM) and anticonvulsant activity in the mouse against NMDA induced convulsions. The ED50 values ranged from 0.22 to 7.76 mg/kg and correlated reasonably well with the Kb determination. In the dibenzo[a,d]cyclohepten-5,10-imine series, the (+)-5S,10R enantiomer displayed consistently higher levels of biological activity. While substitution at the 3-position of (+)-10 with electronegative atoms generally increased in vitro activity, a loss of potency relative to (+)-10 (MK-801) was observed in vivo for all of the compounds tested.

Animals↗
PubMed1976

Evaluation of six short term tests for detecting organic chemical carcinogens and recommendations for their use.

Six short term tests for detecting carcinogenicity have been evaluated using 120 compounds, of which half were carcinogens and the rest non-carcinogens. The results obtained indicate that the Ames test and a "cell transformation" assay are both sufficiently sensitive to carcinogenicity, or the lack of it, in the compounds studied to enable them to be employed for detecting potential carcinogens. The consequences of using short term tests under various screening conditions have been explored. In order to have confidence in the results obtained for new or previously untested compounds it is important to use such tests in a carefully controlled manner.

Alkylating Agents↗
PubMed1997

[Comparison of 4 extraction methods of chemical constituents in medicinal tea sishen chaji].

Four extraction method for the medicinal tea Sishen Chaji, were compared with psoralen, schizandrin B and evodiamine taken as indexes. The result shows that the total contents of the three compounds decrease progressively in the following order: semi-bionic extraction, semi-bionic extraction by precipitation with alcohol, extraction with water, and extraction with water and precipitation with alcohol.

Cyclooctanes↗
PubMed1990

[Chemical and biological characterization of electrofilter dust from a waste incinerating plant. 2. Mutagenic activity of organic extracts and their subfractions and determination of the PAH content].

In a recent study, we showed that the Soxhlet extraction with toluene and pretreatment with diluted HCl is the best suitable method to remove organic compounds from particles collected by electrostatic precipitation in municipal waste incinerators. In the present paper, the mutagenic activity of the extracts from particulate samples were studied, using strain TA 100 as a tester strain. A small if any mutagenic activity was observed from most of the samples. The highest mutagenic effects were observed at different extract concentrations and without metabolic activation. A fractionation technique was developed and subfractions (dichlormethane and dichlormethane/methanol) were tested for their mutagenic potential and PAH-content. Small amounts of polycyclic aromatic hydrocarbons (PAH) were found, which were concentrated to an extent of 90% on the dichlormethane fraction. The results showed a tendency of reactivity to concentrate in the polar fraction.

Chemical Fractionation↗
PubMed2006

Cyanoacetic acid hydrazones of 3-(and 4-)acetylpyridine and some derived ring systems as potential antitumor and anti-HCV agents.

Two new acetylpyridinehydrazones derived from cyanoacetic acid hydrazide have been synthesized namely: cyanoacetic acid (1-pyridin-3 or 4-yl-ethylidene) hydrazides (1a,b). and some derived ring systems: 2-imino or 2-oxo-2H-chromenes (2a,b and 3a,b), substituted 2-thioxo-2,3-dihydrothiazoles (4a-d), substituted 2-thioxo-2,3-dihydro-6H-thiazolo[4,5-d]pyrimidin-7-ones (5a-d), substituted dihydrothiazoles (7a,b), and substituted 2-oxo-1,2-dihydropyridines (8a-d and 9a,b). Fifteen compounds were evaluated for their anticancer activity using the USA-NCI in-vitro screening program. Among the tested compounds, 8d exhibited a high value of percent tumor growth inhibition at concentrations of 10(-5) to 10(-7) M in all cancer cell lines, while 8b exhibited a significant value of percent tumor growth inhibition at concentration <10(-8 )M against non-small cells lung HOP-92. In addition, nine compounds were investigated for their in-vitro effect on the replication of hepatitis-C virus (HCV) in HepG2 hepatocellular carcinoma cell line infected with the virus using the reverse transcription polymerase chain reaction technique. Six compounds were capable of inhibiting the replication of both the HCV RNA (+)- and (-)-strands at 5-100 microg/mL concentration range. The activity order was 7b > 1b = 3a > 4c > 7a > 5c.

Antineoplastic Agents↗
PubMed2006

Monocyclic and dicyclic hydrocarbons: structural requirements for proximal giant axonopathy.

The chromogenic and neurotoxic gamma-diketone 1,2-diacetylbenzene (1,2-DAB), but not its isomer 1,3-DAB, induces blue discoloration of tissues and urine, clustering of axonal microtubules and proximal neurofilament-filled axonal swellings in rodents. The remarkable chromogenic property of 1,2-DAB, a monocyclic aromatic hydrocarbon, arises from reaction with lysine residues of proteins and formation of dimeric and polymeric derivatives. Tetralin, a dicyclic solvent structurally related to acetyl ethyl tetramethyl tetralin, a chromogenic and neurotoxic agent, reportedly induces excretion of green urine, and causes neurological disturbances in humans. Monocyclic aromatic 1,2,4-triethylbenzene (1,2,4-TEB), but not its isomer 1,3,5-TEB, is also reportedly chromogenic and induces neurophysiological deficits in rodents consistent with axonal neuropathy, but without neuropathological confirmation. We treated 12-week-old C57Bl/6 mice by gavage with 300, 600, or 900 mg/kg/day 1,2,4-TEB, or equivalent doses of 1,3,5-TEB, 3 days/week, for up to 12 weeks, or intraperitoneally with 400 mg/kg/day tetralin, or 50 or 100 mg/kg/day of its alpha-tetralol analogue, 5 days/week, for up to 5 weeks. Animals treated with 1,2,4-TEB, but not 1,3,5-TEB, tetralin or alpha-tetralol, developed hind limb weakness, excreted greenish urine, and showed 1,2-DAB-like neuropathology. These findings support the hypothesis that 1,2-spaced ethyl (or acetyl) moieties on a benzene ring of hydrocarbons are required for hydrocarbons to induce chromogenic changes and proximal giant neurofilamentous axonopathy. Key molecular targets of these compounds likely reside in the axon where they serve to maintain normal cytoskeletal organization.

Animals↗
PubMed1992

KS-505a, a novel inhibitor of bovine brain Ca2+ and calmodulin-dependent cyclic-nucleotide phosphodiesterase from Streptomyces argenteolus.

A novel compound, KS-505a was isolated from the culture broth of a strain identified as Streptomyces argenteolus A-2. The compound inhibited bovine brain Ca2+ and calmodulin-dependent cyclic-nucleotide phosphodiesterase with an IC50 value (the concentration causing 50% inhibition) of 0.065 microM. The compound around that concentration had little or no effect on heart calmodulin-dependent and -independent cyclic-nucleotide phosphodiesterases, and protein kinase C.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Novel inhibitors of fungal protein synthesis produced by a strain of Graphium putredinis. Isolation, characterisation and biological properties.

The isolation and structure determination of 6 analogues of the fungal protein synthesis inhibitor GR135402, from Graphium putredinis, is described. The relative potencies of the compounds as protein synthesis inhibitors and as in vitro antifungal agents provide interesting insights into the structure-activity relationships in this series.

Antifungal Agents↗
PubMed1985

Metabolism and effects of organic compounds in animals.

In recent years, society has become increasingly aware and concerned about protection from chemicals released into the environment. The knowledge of the metabolism and effects of organic compounds in animals, specifically food-producing animals, are of paramount importance in assessing potential human health hazards. An intensive effort has been directed at detection of chemicals in the environment, determination of their physiological insult and cellular interaction; in particular their carcinogenic and mutagenic induction capability. The chemical exposure of food-producing animals can be extremely difficult to evaluate and quite devastating. The exposure of food-producing animals to polybrominated biphenyls (PBBs) and polychlorinated biphenyls (PCBs) emphasizes the seriousness of the problem. The polycyclic aromatic hydrocarbons (PAHs), capable of inducing cancer in experimental animals, have been studied extensively in laboratory animals. Current studies deal with the mechanism of metabolism of PAHs and the ultimate carcinogenic form. Although our knowledge concerning the health hazards of organic chemicals is continually increasing, its impact on food-producing animals and man's food chain is poorly understood. Awareness of the problem by practicing veterinarians and toxicologists, environmental toxicologists and public health officials is required to evaluate the impact of organic chemicals on the human food chain.

Animals↗
PubMed1984

Toxicological and chemical characterization of the process stream materials and gas combustion products of an experimental low-btu coal gasifier.

The process gas stream of an experimental pressurized McDowell-Wellman stirred-bed low-Btu coal gasifier, and combustion products of the clean gas were characterized as to their mutagenic properties and chemical composition. Samples of aerosol droplets condensed from the gas were obtained at selected positions along the process stream using a condenser train. Mutagenicity was assessed using the Ames Salmonella mammalian microsome mutagenicity assay (TA98, with and without rat liver S9). All materials required metabolic activation to be mutagenic. Droplets condensed from gas had a specific mutagenicity of 6.7 revertants/microgram (50,000 revertants/liter of raw gas). Methylnaphthalene, phenanthrene, chrysene, and nitrogen-containing compounds were positively identified in a highly mutagenic fraction of raw gas condensate. While gas cleanup by the humidifier-tar trap system and Venturi scrubber led to only a small reduction in specific mutagenicity of the cooled process stream material (4.1 revertants/microgram), a significant overall reduction in mutagenicity was achieved (to 2200 revertants/liter) due to a substantial reduction in the concentration of material in the gas. By the end of gas cleanup, gas condensates had no detectable mutagenic activity. Condensates of combustion product gas, which contained several polycyclic aromatic compounds, had a specific mutagenicity of 1.1 revertants/microgram (4.0 revertants/liter). Results indicate that the process stream material is potentially toxic and that care should be taken to limit exposure of workers to the condensed tars during gasifier maintenance and repair and to the aerosolized tars emitted in fugitive emissions. Health risks to the general population resulting from exposure to gas combustion products are expected to be minimal.

Air Pollutants↗
PubMed1992

Differential effects of the protein kinase C inhibitors H7 and calphostin C on the cell cycle of neuroblastoma cells.

We have studied the effect of protein kinase C inhibitors 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) and calphostin C on the cycle of Neuro-2a cells. Both compounds inhibited cell proliferation and DNA synthesis. Transition from G2 to M phase was not altered by these compounds. Calphostin C blocked the cells in G0/G1, while H7 did not at any specific point in the cell cycle. We also show that the antiproliferative effect induced by both inhibitors is reversible.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2006

Glutathione S-tranferases and cytochrome P450 activities in Mytilus galloprovincialis from the South coast of Portugal: effect of abiotic factors.

To assess the health of aquatic organisms, biomarkers that measure changes at the biochemical level have been used as effective early warning tools in ecological risk assessment. In order to develop an integrated risk assessment strategy for the south coast of Portugal, mussels Mytilus galloprovincialis were collected from six sites along the coast with different organic contaminant characteristics. Additionally, an active biomonitoring approach was followed by transplanting indigenous mussels from site 4 to 6 and vice versa (from site 6 to 4) for 28 days. PAHs and PCBs contents were measured and the associated responses of phase I and phase II detoxification mechanisms evaluated by measuring cytochrome P450 and GST activities. GST activity was also determined on different tissues (gills, digestive gland, foot, mantle and gonads) of M. galloprovincialis and the impact of abiotic parameters (temperature, salinity, pH, conductivity and dissolved oxygen) on the GST activity assessed. Results indicate that CYP 450 follow the same pattern of PAHs and a direct relationship exist between CYP 450 and PAH levels from the different sites. Although there is a decrease between GST and PAHs concentrations it was not significant. The majority of the GST activity was in the gills and the digestive gland (around of 75% of the activity measured in all tissues) followed in decreasing order by the mantle, gonads. An inverse relationship between GST activity and salinity was detected along with temperature although not significant. These two biomarkers respond to changes of these two groups of compounds and to salinity especially for GST. In conclusion CYP 450 in mussels gives a reliable response as biomarker for organic contaminants in risk assessment in the South Coast of Portugal.

Animals↗
PubMed1976

[Water pollution and carcinogenic risks].

The main subjects emphasized in this contribution are the following ones: 1 - To investigate the presence of cancerogenic compounds derived directly or by transformations within trophic chains from domestic and industrial effluents. 2 - To evaluate potential cancerogenic health hazards due to polluted a quatic environement. The following substances might be regarded as to be cancerogenic: nitros amins, mycotoxins, complex organic and inorganic compounds and synthetic organicals. Based on epidemiological and epizoonic evidences, as well as human and experimental pathology, the relevant importance of particular group of compounds is evaluated. Presented evaluation is indicating that the water-borne cancerogenesis might be of an important significance. Therefore, the needs for essential increase in relevant research, implemented by advanced methods, which can cope with complexity of ecological processed, are stressed and further efforts recommended.

Animals↗
PubMed1988

Mutagenicity of bi-, tri- and tetra-cyclic aromatic hydrocarbons in the "taped-plate assay" and in the conventional salmonella mutagenicity assay.

Aromatic hydrocarbons in the range of 1-4 nuclear rings were examined for mutagenicity in the so-called "taped-plate assay". This modification of the Ames assay is particularly equipped for the detection of volatile mutagens. Of the many compounds tested only phenanthrene, pyrene, benzo[c]phenanthrene and benzoacenaphthylene were positive in this assay. The present data underline the exceptional behaviour of fluoranthene by being a rather potent bacterial mutagen with a volatile nature (as found in a previous study).

Animals↗
PubMed2006

Facile transformation of benzocyclobutenones into 2,3-benzodiazepines via 4pi-8pi tandem electrocyclic reactions involving net insertion of diazomethylene compounds.

Efficient transformations of benzocyclobutenones into 2,3-benzodiazepines by a formal insertion of diazomethylene compounds are described. This sequential process includes nucleophilic addition of diazomethylene anion, oxy-anion accelerated o-quinodimethane formation by an electrocyclic ring-opening reaction, and 8pi-electrocyclization in one-pot under remarkably mild conditions. Intermediary oxy-anion plays an important role for the efficient transformations.

Benzodiazepines↗
PubMed1990

Extracts of airborne particulates collected at different locations in the Copenhagen area induce the expression of cytochrome P-450IA1.

Acetone extracts of airborne particulates collected at different sites in the greater Copenhagen area were tested for their ability to induce the expression of cytochrome P-450IA1 RNA in a human breast cancer cell line, T47-D. The induction efficiency was expressed as an benz[a] anthracene equivalents, that is, the amount of benz[a]anthracene required to give the same level of induction. A significantly higher level of induction of P-450IA1 RNA was seen with samples collected on days with a smog alert. The inducibility of samples collected in rural areas was lower, but no significant difference in inducibility was found between samples collected in urban and suburban areas. Lack of correlation between the mutagenic activity in the Ames assay and the P-450IA1-inducing activity of the samples suggests that the complex mixture of compounds found in airborne particulates may have different biological activities in the two short-term test systems. Measurements of P-450IA1 inducibility provide a new, sensitive approach to assess the biological activity of material present in air pollution. The presence in airborne particulates of chemical compounds that induce cytochrome P-450IA1 an enzyme responsible for the metabolism of ubiquitous chemical carcinogens, suggests that the general environment may change an individual's response to the impact of exogenous chemicals, including the carcinogens present in cigarette smoke.

Air Pollutants↗
PubMed1990

[Animal experiment and in vitro studies with inhaled environmental pollutants].

Risk assessment of inhaled toxicants is a critical treatise in inhalation toxicology. In particular, the extent of extrapolation from animal experiments to the human situation is frequently influenced by such factors as the method of application (Implantation, instillation or inhalation) and species-specific differences. This difficulty becomes especially conspicuous when the carcinogenicity is to be determined after the inhalation of, for example, diesel engine exhaust, coal oven flue gas, or cadmium compounds. Nowadays, in-vitro techniques are also available for successfully investigating the metabolism of hazardous compounds and thereby-induced DNA damage in animal and human airway epithelial cells; results gained through the employment of these techniques will, at all events, bear increasing weight in terms of the valuation and assessment of risks to humans.

Air Pollutants↗