SEARCH · PubMed Health

Results for “Cyclohexanones”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 37 records · Page 2Linked to original sources

PubMed1988

Effect of cyclohexanone derivatives on percutaneous absorption of ketoprofen and indomethacin.

The promoting effect of cyclohexanone derivatives on the percutaneous absorption of ketoprofen and indomethacin from gel ointments was investigated in rats. Drug absorption was markedly enhanced by the addition of 2-tert-butylcyclohexanone. Promoting activities of 2,6-dimethyl and 4-tert-butylcyclohexanone were also observed, but their effects were significantly lower than that of the 2-tert-butyl derivative. The effect of side chain length at the 2-position of the cyclohexanone ring on the percutaneous absorption of these drugs was determined similarly using a series of 2-n-alkylcyclohexanones. Pronounced effects were observed in the case of 2-n-octylcyclohexanone, suggesting that a chain length of eight carbons is an important factor for absorption enhancement in this series. The extent of absorption enhancement was found to be an almost linear function of 2-n-octycyclohexanone concentrations in the range from 0 to 10%.

Administration, Cutaneous↗

PubMed1976

Evaluation of 2-benzylidenecyclohexanones and 2,6-bis(benzylidene)cyclohexanones for antitumor and cytotoxic activity and as inhibitors of mitochondrial function in yeast: metabolism studies of (E)-2-benzylidenecyclohexanone.

Some 2-benzylidenecyclohexanones, 2,6-bis(benzylidene)cyclohexanones, and related compounds were evaluated for antitumor and cytotoxic activities; (E)-2-benzylidenecyclohexanone (Ia) was shown to have significant cytotoxic properties and a potent inhibitory effect on yeast mitochondria. After intraperitoneal injection of Ia, unchanged drug and a metabolite, tentatively identified as 2-(p-hydroxybenzyl)cyclohexanol, were found in the urine. No metabolites were found in the feces. Oral administration of Ia afforded three unidentified metabolites in the urine and three unidentified metabolites in the feces.

Animals↗

PubMed1992

Synthesis and cytotoxic evaluation of some 6-arylidene-2-(alpha-hydroxyamino-alpha-arylmethyl)cyclohexanone oximes and related compounds.

Reaction of 2,6-bis-(phenylmethylene)cyclohexanone (1) with a 4-molar excess of hydroxylamine hydrochloride and sodium acetate to produce the corresponding oxime 2 gave rise to 2-(alpha-hydroxyamino-alpha-phenylmethyl)-6-phenylmethylenecyclohexan one oxime (5a), whose structure was deduced from high-resolution proton nuclear magnetic resonance spectroscopy and confirmed by X-ray analysis. Compound 2 was eventually prepared from 1 with hydroxylamine per se and not with a mixture of hydroxylamine hydrochloride and sodium acetate. Ten analogues of 5a, namely 5b-5k, were prepared and evaluated for cytotoxicity. Six of the 11 compounds in series 5, as well as 1, showed activity in the 240-950 microM range against murine mammary EMT6 cells. Series 5 was also examined for cytotoxicity in an in vitro screen conducted by the National Cancer Institute with approximately 54 cell lines, and four compounds demonstrated selective toxicity toward various groups of tumors.

Animals↗

PubMed1985

Effects of (1,6-di(O-carbamoyl)cyclohexanone oxime)hexane (RHC 80267) on prostaglandin biosynthesis and accumulation of diacylglycerol and arachidonic acid in rabbit iris.

The effects of RHC 80267, (1-6-di(O-carbamoyl)cyclohexanone oxime)hexane, a diacylglycerol (DG) lipase inhibitor, on the DG lipase pathway and on arachidonic acid (AA) metabolism were investigated in the iris muscle. Incubation of the iris for 30 min at 37 degrees resulted in a loss of AA from phosphatidylinositol, phosphatidylcholine, and phosphatidylethanolamine of 40, 25, and 32% respectively. It was found that the drug inhibited the activity of DG lipase in the iris microsomal fraction and it increased the accumulation of DG, AA and other glycerolipids in iris muscle prelabeled with [14C]AA, presumably by inhibiting this enzyme. Under the same experimental conditions, the drug increased the accumulation of DG and AA in the tissue in a dose- and time-dependent manner, and it inhibited the synthesis of prostaglandin E2 (PGE2) and PGF2 alpha by iris and iris microsomes in a dose-dependent manner. The data presented indicate that RHC 80267 has nonspecific effects on glycerolipid and AA metabolism in this tissue. We conclude that, while the drug does inhibit DG lipase in the intact iris, the present findings that it increased the accumulation of glycerolipids and AA and that it inhibited the biosynthesis of PGs in this tissue throw some doubt on its use in studies on the mechanism of AA release from membrane phosphoinositides for PG synthesis.

Animals↗

PubMed1985

Toxicity of cyclohexanone oxime. I. Hematotoxicity following subacute exposure in rats.

Cyclohexanone oxime (CHO) was given po to male and female Fischer 344 rats at dose levels of 10, 25, 75, 150, and 300 mg/kg, five times a week for a period of 2 weeks. Control animals received distilled water. All animals given intermediate dose levels (10, 25, 75, and 150 mg/kg) and one half of the animals which were dosed at the high dose (300 mg/kg) as well as one half of the controls were terminated 14 days after administration of the first dose. The remaining rats received no treatment for an additional 14 days and were sacrificed on Day 28 of the study (recovery phase). Dose-related decreases in erythrocyte number, hemoglobin, and hematocrit, with an accompanying increase in reticulocytes and circulating nucleated erythrocytes, were observed in both sexes at Day 14. Methemoglobin levels, determined only at the high dose, were elevated in both sexes at this time. Splenomegaly and hepatomegaly were observed in both sexes at 14 and 28 days. Histopathological examination of the spleen and bone marrow revealed dose-related erythroid hyperplasia at 14 days which subsided by Day 28. The above effects were more pronounced in males. Erythrocyte numbers were only slightly depressed and reticulocytes mildly elevated in males at Day 28. Hematological values were not statistically different from controls in females at this time. These results suggest that CHO induces oxidative damage to the erythrocyte, resulting in a hemolytic anemia accompanied by increased erythropoiesis. The toxic effects appear reversible upon cessation of exposure.

Anemia, Hemolytic↗

PubMed1985

Toxicity of cyclohexanone oxime. II. Acute dermal and subchronic oral studies.

Dermal exposure of rabbits to cyclohexanone oxime (CHO) for 24 hr at 0, 0.8, 2, and 5 g/kg caused dose-related reticulocytosis on the day after dosing as well as a decrease in hemoglobin in the 5-g/kg females 7 days postdosing. Gavage of rats 5 days a week for 13 weeks at levels of 0, 0.25, 2.5, and 25 mg/kg resulted in a dose-related decrease in erythrocyte number, hemoglobin, and hematocrit, with an accompanying increase in circulating reticulocytes and nucleated erythrocytes, in both sexes. Also seen were corneal opacities and an increased incidence of Howell-Jolly bodies. Results suggested an increased erythropoiesis in the spleen and bone marrow. The data from satellite groups terminated at 30 and 60 days revealed no effect at the lower test level, but results from the end of the study showed a clear cumulative dose response down to the 0.25-mg/kg level. Males were affected earlier and at lower doses than females. These results, along with those of a subacute study with a recovery period, suggest that CHO induces an oxidative attack on erythrocytes which appears reversible upon cessation of exposure.

Administration, Oral↗

PubMed1975

Deuterium transfer from [1,1-2-H] ethanol during metabolism of bile acids and cyclohexanone in the isolated perfused rat liver.

Deuterium transfer from [1,1-2-H]ethanol (95 atoms % excess) to reducible substrates was studied in the isolated perfused rat liver. The dueterium excess in cyclohexanol formed from cyclohexanone was somewhat lower (49 atoms%) than found under conditions in vivo, and this was also true of the deuterium excess in lithocholic acid formed from 3-oxo-5beta-cholanoic acid. These results may reflect a slower rate of ethanol oxidation in the isolated organ than in vivo. Cycloserine decreased the dueterium transfer to both substrates, whereas addition of lactate and malate resulted in an increased deuterium excess in cyclohexanol and a decreased deuterium excess in lithocholic acid. Addition of heavy water to the perfusion fluid resulted in labelling at C-3 of lithocholic acid formed from 3-oxo-5beta-cholanoic acid, and at C-3, C-4 and C-5 of 3alpha-hydroxy-5alpha-cholanoic acid formed from 3-oxo-4-cholenoic acid. The deuterium excess of hydrogens derived from NADPH (at C-3 and C-5) was approximately the same as that of hydrogen derived directly from water (at C-4). Thus, the hydrogen of NADPH is extensively exchanged with protons of water, which explains the dilution of deuterium with protium during the transfer from [1,1-2-H]ethanol via NADPH to the bile acids. The labelling at C-5 in the reduction of the 4,5-double bond indicates that different pools of NADPH are used for reduction of this double bond and the 3-oxo group, since in a previous study it was shown that deuterium is transferred from [1,1-2-H]ethanol only in the latter reaction.

Animals↗

PubMed1989

Fetal effects of inhalation exposure to cyclohexanone vapor in pregnant rats.

Cyclohexanone (CH), a solvent and thinner that has extensive use in industry, was investigated for developmental effects using pregnant Sprague-Dawley rats exposed to 100, 250 or 500 ppm concentrations in an inhalation chamber for seven hours per day from days 5 through 20 of pregnancy. Controls were exposed to room air. Maternal weight gain at 250 and 500 ppm CH was only slightly lower than in the control dams, and a grey mottling of the lungs was seen in a few of the CH-exposed dams. There were no significant differences between the CH and control groups in fetal weight, resorption sites, fetal death or sex ratio. External and soft tissue examinations revealed no significant incidence of malformations or variations in CH-exposed animals. A slight increase in the mean percent of rudimentary ribs per litter was observed in the 250 and 500 ppm CH-exposed groups. However, no significant numbers of skeletal malformations were noticed in either the CH or room air control groups. It was concluded that respiratory exposure of rats to as much as 500 ppm CH during organogenesis was unlikely to be developmentally toxic.

Administration, Inhalation↗

PubMed1982

Studies on the chirality of sulfoxidation catalyzed by bacterial flavoenzyme cyclohexanone monooxygenase and hog liver flavin adenine dinucleotide containing monooxygenase.

The stereochemical outcome of oxygen transfer to the sulfur moiety of aryl alkyl sulfides catalyzed by two flavoenzyme monooxygenases has been determined by resolution of sulfoxide product enantionmers on a high-pressure liquid chromatography column [Pirkle, W. H., Finn, J. M. Schreiner, J. L., & Hamper, B. C. (1981) J. Am. Chem. Soc. 103, 3964-3966] containing a 3,5-dinitrobenzoyl-D-phenylglycine chiral stationary phase. With 4-tolyl ethyl sulfide as substrate, cyclohexanone monooxygenase from Acinetobacter produces predominantly the (S)-(-)-sulfoxide (82% S, 18% R), a modest enantioselectivity. In contrast, the flavin adenine dinucleotide (FAD) containing a monooxygenase purified from hog liver microsomes carries out sulfoxidation to yield the (R)-(+)-sulfoxide enantiomer as major product (95% R, 5% S). The presence of the minor sulfoxide enantiomer in each case appears to be due to incomplete chiral processing by each enzyme and not to a competing, achiral, nonenzymic sulfoxidation process. The mammalian FAD-containing monooxygenase also oxygenates the divalent sulfur of the antiarthritic drug sulindac sulfide to yield a single dextrorotatory isomer of the sulfoxide prodrug. Analysis of the chiral outcome of sulfoxidation catalyzed by rat liver microsomes indicated that phenobarbital treatment increases the capacity for S-(-)-oxygenation of 4-tolyl ethyl sulfide, suggesting that the phenobarbital-induced cytochrome P-450 isoenzymes catalyze formation of the (S)-(-)-sulfoxide preferentially, a surmise validated in the following paper [Waxman, D. J., Light, D. R., & Walsh, C. (1982) Biochemistry (following paper in this issue)]. With sulindac sulfide as substrate, though, both control and phenobarbital-induced microsomes catalyze sulfoxidation to yield the same (+)-sulfoxide enantiomer generated by the purified FAD-containing monoxygenase, suggesting a low degree of participation by the cytochrome P-450 isozymes in sulfoxidation of this compound.

Acinetobacter↗

PubMed1976

The purification and properties of cyclohexanone oxygenase from Nocardia globerula CL1 and Acinetobacter NCIB 9871.

1. Cyclohexanone oxygenases from Norcardia globerula CL1 and Acinetobacter NCIB 9871 have been purified 12-fold and 35-fold respectively and each gives a single symmetrical sedimentation peak in the ultracentrifuge and a single protein band on 2.25 nm average pore radius polyacrylamide gels. 2. The enzyme from N. globerula has a molecular weight of 53000 while that from Acinetobacter has a molecular weight of about 59000. Each is a single polypeptide chain with one mole of bound FAD per mole of protein that does not dissociate during purification. Acidification of the Acinetobacter enzyme in the presence of (NH4)2SO4 releases the bound FAD and yields native apoenzyme from which the active holoenzyme can be reconstituted. The apparent dissociation constant for the FAD is 40 nM.

Acinetobacter↗

PubMed1988

Acinetobacter cyclohexanone monooxygenase: gene cloning and sequence determination.

The gene coding for cyclohexanone monooxygenase from Acinetobacter sp. strain NCIB 9871 was isolated by immunological screening methods. We located and determined the nucleotide sequence of the gene. The structural gene is 1,626 nucleotides long and codes for a polypeptide of 542 amino acids; 389 nucleotides 5' and 108 nucleotides 3' of the coding region are also reported. The complete amino acid sequence of the enzyme was derived by translation of the nucleotide sequence. From a comparison of the amino acid sequence with consensus sequences of nucleotide-binding folds, we identified a potential flavin-binding site at the NH2 terminus of the enzyme (residues 6 to 18) and a potential nicotinamide-binding site extending from residue 176 to residue 208 of the protein. An overproduction system for the gene to facilitate genetic manipulations was also constructed by using the tac promoter vector pKK223-3 in Escherichia coli.

Acinetobacter↗

PubMed1976