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At least 145 records · Page 8Linked to original sources
PubMed2005

Synthesis and antitumor activity of some curcumin analogs.

In this study, four new curcurmin analogs (compounds 1, 2, 17 and 18) were synthesized. 17 [3,5-bis(4-hydroxy-3-methoxy-5-methylcinnamyl)N-methylpiperidone] showed high activity with GI50, TGI, and LC50 MG-MID values of 21.3, 70.7, and 97.7 microM, respectively. 18 [3,5-bis(4-hydroxy-3-methoxy-5-methylcinnamyl)-N-ethylpiperidone] showed the highest activity in this study with GI50, TGI, LC50 MG-MID values of 4.4, 33.8, 89.1 microM, respectively. 18 is even more active than curcumin with GI50, TGI, LC50 MG-MID values of 38.4, 35.6, 66.0 microM; respectively. 8 showed moderate selectivity towards Leukemia cell line-subpanel with a ratio of 5.6 (curcumin ratio: 1.2 for the same subpanel). The in vitro anti-tumor screening reveals that the results go hand in hand with the in vitro free radical scavenging effects. The antioxidant effect of these compounds depends mainly on the stabilization of the formed phenoxy free radical for which the p-hydroxy phenyl moiety is essential. o-substitution by electron-donating groups like the o-methoxy group (and to a even higher degree by the ethoxy group) increases the stability of phenoxy free radical, hence increasing both free scavenging and anti-tumor effects. Increasing the alkyl group chain on the N in the series of substituted N-alkyl piperidones as well as the extension of conjugation, increases the stabilization of phenoxy free radical and thereby the activity towards both free radical scavenging and anti-tumor effects. This may be attributed to an increased positive inductive effect and/or increased lipophilicity of the new compounds, a fact which is proven by the superior activities of compounds 17 and 18.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Curcumin analogs as potent aldose reductase inhibitors.

In the present study, curcuminoids isolated from curcuma longa were demonstrated to possess inhibitory activities on bovine lens aldose reductase. In order to find more potent aldose reductase inhibitor, curcumin analogs were synthesized and evaluated for their ability to inhibit bovine lens aldose reductase enzyme. The results indicated that the compounds with tetrahydroxyl groups, 2,6-bis(3,4-dihydroxybenzylidene)cyclohexanone (A(2)), 2,5-bis(3,4-dihydroxybenzylidene)cyclopentanone (B(2)), 1,5-bis(3,4-dihydroxyphenyl)-1,4-pentadiene-3-one (C(2)), and 3,5-bis(3,4-dihydroxybenzylidene)-4-piperidone (D(2)) showed remarkably potent inhibitory effects on aldose reductase with IC(50) of 2.9 microM, 2.6 microM, 3.4 microM, and 4.9 microM, respectively. The structure-activity relationship revealed that the curcumin analogs with ortho-dihydroxyl groups could form a more tight affinity with aldose reductase to exert more potential inhibitory activities.

Aldehyde Reductase↗
PubMed2002

Spin trapping study of reactive oxygen species formation during bopindolol peroxidation.

The generation of singlet molecular oxygen ((1)O(2)) and hydroxyl radicals (HO*) during peroxidation of bopindolol in the presence of Co(II) ions was studied using electron spin resonance (ESR) and spectrophotometry methods. 2,2,6,6-Tetramethyl-4-piperidone and 5,5-dimethyl-1-pyrroline-1-oxide were used as traps. The spectrophotometry determination of (1)O(2) was based on bleaching of p-nitrosodimethylaniline (RNO), which was caused by the product of the reaction of (1)O(2) with imidazole and was followed by monitoring the decrease in optical density at 440 nm. The effect of (1)O(2) quenchers and oxygen free radical scavengers on the ESR signal and the bleaching of RNO was studied. The data presented here give new evidence for generation of the reactive oxygen species during peroxidation of bopindolol.

Electron Spin Resonance Spectroscopy↗
PubMed2006

Dynamic kinetic resolution and desymmetrization processes: a straightforward methodology for the enantioselective synthesis of piperidines.

A straightforward procedure for the synthesis of enantiopure polysubstituted piperidines is reported. It involves the direct generation of chiral non-racemic oxazolo[3,2-a]piperidone lactams that already incorporate carbon substituents on the heterocyclic ring and the subsequent removal of the chiral auxiliary. The key step is a cyclocondensation reaction of (R)-phenylglycinol or other amino alcohols with racemic or prochiral delta-oxo (di)acid derivatives in highly stereoselective processes involving dynamic kinetic resolution and/or desymmetrization of diastereotopic or enantiotopic ester groups.

Ethanolamines↗
PubMed1984

Enhancement of lung-colonizing ability of cloned low-metastatic Lewis lung carcinoma cells by treatment with highly polar compounds.

Treatment of low-metastatic Lewis lung carcinoma cells (P-29) with dimethylsulfoxide (DMSO) in vitro enhanced their lung-colonizing ability. The effects of other highly polar compounds on the lung-colonizing ability of P-29 cells were examined. The following compounds were found to enhance the lung-colonizing ability of the cells: acetamide, N-methylacetamide, N-methylformamide, N,N-dimethylformamide, piperidone and hexamethylphosphoric triamide. Treatment of P-29 cells with DMSO or other polar compounds resulted in increases in activities of degradative enzymes, such as cathepsin B and plasminogen activator. The increases in cathepsin B and plasminogen activator activities were apparent after a 24 h treatment with DMSO and were suppressed by simultaneous treatment with cycloheximide, which suggested that they were due to syntheses of new proteins. DMSO-treated P-29 cells degraded [3H]leucine-labelled subendothelial matrix much more than did untreated cells. P-29 cells treated with DMSO or other polar compounds became attached to culture dishes more rapidly and were more resistant to detachment by trypsin treatment than untreated cells. A significant correlation was found between the degrees of adhesiveness of P-29 cells treated with various polar compounds and their lung-colonizing abilities.

Animals↗
PubMed2005

NMR spectroscopic analysis of new spiro-piperidylrifamycins.

New spiro-piperidylrifamycin derivatives are presented. These compounds were synthesized from the reaction of 3-amino-4-iminorifamycin S and enantiomerically pure 4-piperidones, which generate diasteroisomeric rifabutin analogues with a new stereocentre at the spiranic carbon. The (1)H and (13)C NMR spectra of these new compounds, and also the configuration of the new stereogenic centres, were assigned using 2D NMR spectroscopic techniques. A preliminary study of the (1)H and (13)C NMR spectra of the starting compounds rifamycin S, 3-amino-4-iminorifamycin S and the related rifabutin was also carried out and as a result, their previously published (13)C NMR data were corrected.

Carbon Isotopes↗
PubMed1986

Murine in vivo L-band ESR spin-label oximetry with a loop-gap resonator.

Small mice (approximately 20 g) were anesthetized and placed in a loop-gap resonator of diameter 25 mm resonating at 1.1 GHz. An oxygen-permeable capsule containing 2.5 X 10(-2) M perdeutero 15N TEMPONE (1-oxyl-2,2,6,6-tetramethyl-4-piperidone) in light paraffin oil was implanted in the peritoneal cavity. Electron spin resonance (ESR) spectra from the capsule are sensitive to the concentration of dissolved oxygen and calibration curves are given. The oxygen concentration was found to rise from a value close to zero when the animal breathes air to a level of 220 microM when the animal breaths pure oxygen. It is speculated that this surprisingly high level is related to the effect of the anesthetic on the cardiovascular system. Encapsulation provides a barrier to spin-label reductants and to paramagnetic metal ions that might confound the spin-label oximetric measurements.

Animals↗
PubMed2001

Co-production of microcystins and aeruginopeptins by natural cyanobacterial bloom.

The relationship between Microcystis composition and the production of microcystins and nontoxic peptides in bloom cells, which was regularly collected in Lake Suwa, Japan, in the summer season from 1991 to 1994, was investigated. In order to determine the structures of the nontoxic peptides, we collected large amounts of bloom materials from the same lake on July 23, 1991, and isolated three nontoxic peptides. They were named as aeruginopeptins 917S-A, -B, and -C, and their structures were mainly determined by a mass spectrometry/mass spectrometry (MS/MS) technique as 19-membered cyclic depsipeptides possessing the Ahp (3-amino-6-hydroxy-2-piperidone) moiety. An analysis of the microcystins and aeruginopeptins in the collected blood cells and their Microcystis composition suggested that the M. aeruginosa large cell size produces both microcystins and aeruginopeptins, and the production of both compounds is genetically closely related.

Cell Size↗
PubMed1999

Improved functional recovery of ischemic rat hearts due to singlet oxygen scavengers histidine and carnosine.

There is increasing evidence that reactive oxygen species (ROS) contribute to post-ischemic reperfusion injury, but determination of the specific ROS involved has proven elusive. In the present study electron paramagnetic resonance (EPR) spectroscopy was used in vitro to measure the relative quenching of singlet oxygen (1O2) by histidine and carnosine (beta-alanyl-L-histidine) utilizing the hindered secondary amine 2,2,6,6-tetramethyl-4-piperidone HCl (4-oxo-TEMP). The relative effect of histidine and carnosine on functional recovery of isolated perfused rat hearts was also studied. Functional recovery was measured by left ventricular developed pressure (LVDP), first derivative of left ventricular pressure (dP/dt), heart rate (HR) and coronary flow (CF). EPR measurements and Stern-Volmer plots showed that 400 microM carnosine quenched 1O2 twice as effectively as equimolar histidine in vitro. Moreover, 10 mM histidine improved functional recovery of isolated rat hearts significantly more than 1 mM histidine. Furthermore, 1 mM carnosine improved functional recovery significantly more than equimolar histidine and as effectively as 10 mM histidine. Experiments with 1 mM mannitol, a known hydroxyl radical scavenger, did not show an improvement in functional recovery relative to control hearts, thereby decreasing the likelihood that hydroxyl radicals are the major damaging species. On the other hand, the correlation between improved functional recovery of isolated rat hearts with histidine and carnosine and their relative 1O2 quenching effectiveness in vitro provides indirect evidence for 1O2 as ROS participating in reperfusion injury.

Animals↗
PubMed1978

Lactam utilisation in Aspergillus nidulans: evidence for a fourth gene under the control of the integrator gene intA.

Mutations in the lamA gene of Aspergillus nidulans prevent the conversion of exogenous 2-pyrrolidone (gamma-butyrolactam) to gamma-amino-n-butyrate (GABA) and also prevent the (probably analogous) utilisation of 2-piperidone (sigma-valerolactam). The lamA gene, in linkage group VIII, probably specifies a lactamase but a rôle in lactam uptake cannot be ruled out. lamA is probably under the control of the positive acting regulatory gene intA, which can integrate its expression with the expression of three other genes, specifying acetamidase, GABA transaminase, and GABA permease, respectively.

Aspergillus nidulans↗
PubMed1995

A local lymph-node assay validation study of a structure-activity relationship model for contact allergens.

A structure-activity relationship model for prediction of contact allergenic potential of chemicals had previously been developed. The model had been shown to be able to classify known allergens and nonallergens using data on physicochemical and reactivity parameters of functional groups by discriminant two-value multiple regression analysis. To investigate the model, six selected chemicals which had not been previously investigated for allergenicity were studied with both the model and a murine local lymph-node assay. The same compounds were predicted to be allergens (3-bromo-2-coumaranone, 1-nitrocyclohexene and alpha-acryloyloxy-beta, beta-dimethyl-beta-butyrolactone) and nonallergens (1-carbethoxy-4-piperidone, 6,7-dimethoxy-2-tetralone and 9-acetylanthracene) by both the model and the local lymph-node assay.

Allergens↗
PubMed2000

Evidence that the reactions of nickel in the presence of vitamin C do not produce toxic oxygen intermediates such as hydroxyl but ascorbate and carbon radicals.

A variety of reactions containing different amounts of nickel ions together with vitamin C were prepared and used in spin trapping experiments designed to show nickel is not a Fenton active metal. Carbon based radicals were observed at low ratios of ascorbate to nickel, and ascorbate radical was observed at high ratios of ascorbate to nickel. No buffer effects were observed. There was no evidence for oxygen intermediates as products of the reaction with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) or alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN), seeming to indicate nickel is not a Fenton metal. To test this hypothesis further trapping studies were run with the singlet oxygen trap 2,2,6,6-tetramethyl-4-piperidone hydrochloride, in which dioxygen was found not to affect the formation of carbon radicals. These results help to explain the damage to DNA observed in the presence of vitamin C and nickel in vitro.

Ascorbic Acid↗
PubMed1981

A spin label method for measuring internal volumes in liposomes or cells, applied to Ca-dependent fusion of negatively charged vesicles.

A new spin label - broadening agent system for measuring trapped volumes of vesicles or cells is described. The method seems to be more advantageous than existing procedures when volumes of highly negatively charged vesicles are to be determined. The membrane permeable spin label is TEMPONE (2,2,6,6-tetramethyl piperidone-N-oxyl), and the nonpermeable broadening agent is chromium oxalate (K3Cr(C2O4)3). Absolute values for the trapped volumes down to 0.1% in 0.1 ml can be measured with an accuracy of about +/- (1-10%). The method is used to study the final volume of fused phosphatidylserine vesicles as a function of the temperature at which the Ca-induced fusion takes place.

Animals↗
PubMed1989

ESR evidence for superoxide, hydroxyl radicals and singlet oxygen produced from hydrogen peroxide and nickel(II) complex of glycylglycyl-L-histidine.

ESR studies using spin traps, 5,5-dimethylpyrroline-N-oxide and alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone, revealed that hydroxyl radical adducts are produced by the decomposition of hydrogen peroxide in the presence of nickel(II) oligopeptides. Order of catalytic activities of nickel(II) oligopeptides used in the production of hydroxyl radical adducts was tetraglycine greater than pentaglycine greater than triglycine greater than GlyGly, GlyHis. Ni(II) GlyGlyHis plus hydrogen peroxide produced superoxide in addition to hydroxyl radical adduct. Trapping experiments with 2,2,6,6-tetramethyl-4-piperidone suggested that singlet oxygen was generated by the reaction of hydrogen peroxide with Ni(II) GlyGlyHis, but not in the case of tetraglycine, pentaglycine, triglycine, GlyGly or GlyHis.

Catalysis↗
PubMed1991

Generation and fate of enamines in the microsomal metabolism of cyclic tertiary amines.

Microsomal oxidation of 1-benzylpiperidine (1-BP) and its cis-2,6-dimethyl analog was studied to assess the involvement of endocyclic enamines, in equilibrium with the initially formed iminiums, in the metabolic activation of cyclic tertiary amines such as phencyclidine. Since the iminiums can be trapped with cyanide, the selective prevention by cyanide of the metabolic production of 1-benzyl-3-piperidone from 1-BP implicates the iminium in equilibrium with enamine as the source of this metabolite. In cases where iminium-enamine coupling is sterically prevented, the iminium in equilibrium with enamine species can be studied independently and are found to be more potent metabolism-dependent inactivators of cytochrome P-450 than are the corresponding parent amines. Possible mechanisms for biological oxidation of cyclic enamines to reactive intermediates are considered.

Amines↗
PubMed1995

Effect of the antiretroviral agent hypericin on rat liver mitochondria.

The photosensitizing effect of hypericin (HY), an antiretroviral agent, on the functions of isolated rat liver mitochondria has been investigated. The respiratory control ratio (RCR), ADP/O and membrane potential of mitochondria were decreased by HY in a light-dependent manner. Uncoupled respiration of mitochondria in the presence of succinate was also inhibited by HY in a light-dependent manner. The ID50 of hypericin for these inhibitions was approximately 0.5 microM. These inhibitory effects of HY were not observed when photosensitization was conducted under anaerobic conditions and were not affected by desferrioxamine (DSF) or superoxide dismutase (SOD). Upon photosensitization of HY, mitochondria consumed oxygen in the absence of respiratory substrate with concomitant formation of thiobarbituric acid reactive substance (TBARS). The amount of oxygen consumed was 100-times greater than that of TBARS formed. The oxygen uptake was partially inhibited by NaN3, and formation of TBARS was inhibited by DSF. Upon photosensitization of HY in the presence of mitochondrial membranes, the electron spin resonance (ESR) signal of 2,2-dimethyl-5-hydroxy-1-pyrrolidinyloxyl (DMPO/.OH) was increased by a mechanism which was suppressed by DSF. An ESR signal for singlet oxygen bound to 2,5-dimethylfuran, 2,2,6,6-tetramethyl-4-piperidone (TEMP) was also detected under light in the presence of mitochondria. This signal of the TEMP-N-oxyl radical (TEMPO) was decreased by azide, which physically quenches singlet oxygen, but was increased by DSF. These results indicate that HY might inhibit mitochondrial functions by a type II photodynamic mechanism but that lipid peroxidation of biological membranes through an active oxygen-mediated photodynamic mechanism is not involved.

Animals↗
PubMed1979

Amino-acid metabolism and liver ultrastructure in hyperornithinemia with gyrate atrophy of the choroid and retina.

Three patients with the rare hyperornithinemia with gyrate atrophy of the choroid and retina (HOGA) syndrome were studied to elucidate the metabolic derangement and its pathologic concomitants. Tenfold elevations of blood ornithine levels, decreases in lysine levels, and hitherto unreported decreases in blood glutamate and glutamine concentration were observed. The output of ornithine from muscle kidney and splanchnic beds was curtailed or reversed after intravenous glucose. Levels of ornithine in venous blood declined after oral glucose, and rose after intravenous arginine. Increased amounts of 3-amino-2-piperidone were found in the urine, but these did not increase after the arginine-induced increase in ornithine levels. Liver biopsies in two patients revealed a marked alteration in mitochondrial ultrastructure. These studies extend the knowledge of the metabolic and pathologic derangements in HOGA. These findings are consistent with a disorder of ornithine-ketoacid transaminase, but such a disorder might not account for all the observations.

Adult↗
PubMed1976

Reaction of nitrosamines in the Udenfriend system: principal products and biological activity.

Reaction of diethylnitrosamine in the non-enzymatic, ascorbic acid-dependent, hydroxylating system of Udenfriend yielded N-nitroso-2-(ethylamino)-ethanol as the major product extracted into methylene chloride. The major product derived from nitrosopiperidine in the same system was N-nitroso-4-piperidone. These products, however, were mutagenic to Salmonella typhimurium TA 1535 only when activated by a rat liver microsomal preparation.

Animals↗