Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Benzophenones”

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 1,117 records · Page 62Linked to original sources
PubMed2001

Multiplexed molecular interactions of nuclear receptors using fluorescent microspheres.

BACKGROUND: We describe a novel microsphere-based system to identify and characterize multiplexed interactions of nuclear receptors with peptides that represent the LXXLL binding region of coactivator proteins. METHODS: In this system, individual microsphere populations with unique red and orange fluorescent profiles are coupled to specific coactivator peptides. The coactivator peptide-coupled microsphere populations are combined and incubated with a nuclear receptor that has been coupled to a green fluorochrome. Flow cytometric analysis of the microspheres simultaneously decodes each population and detects the binding of receptor to respective coactivator peptides by the acquisition of green fluorescence. RESULTS: We have used this system to determine the binding affinities of human estrogen receptor beta ligand binding domain (ERbeta LBD) and human peroxisome proliferator activated receptor gamma ligand binding domain (PPARgamma LBD) to a set of 34 coactivator peptides. Binding of ERbeta LBD to a coactivator peptide sequence containing the second LXXLL motif of steroid receptor coactivator-1 (SRC-1(2) (676-700) is shown to be specific and saturable. Analysis of receptor binding to a multiplexed set of coactivator peptides shows PPARgamma LBD binds with high affinity to cAMP response element binding protein (CBP) peptides and to the related P300 peptide while ERbeta LBD exibits little binding to these peptides. Using the microsphere-based assay we demonstrate that ERbeta LBD and PPARgamma LBD binding affinities for the coactivator peptides are increased in the presence of agonist (estradiol or GW1929, respectively) and that ERbeta LBD binding is decreased in the presence of antagonist (raloxifene or tamoxifen). CONCLUSIONS: This unique microsphere-based system is a sensitive and efficient method to simultaneously evaluate many receptor-coactivator interactions in a single assay volume. In addition, the system offers a powerful approach to study small molecule modulation of nuclear receptor binding.

Amino Acid Motifs↗
PubMed2001

Ras-mediated cleavage of a GTP analogue by a novel mechanism.

The small guanosine triphosphate (GTP) binding protein Ras is involved in many cellular signal transduction processes leading to cell growth, differentiation and apoptosis. Mutations in ras genes are found in a large number of human tumours. GTP hydrolysis, the process that normally leads to the transition of the Ras protein from the active (GTP-bound) form to the inactive (GDP-bound) form is impaired due to these oncogenic mutations. In contrast, the GTP analogue 3,4-diaminobenzophenone(DABP)-phosphoramidate-GTP, a substrate for GTP-binding proteins, enables switching to the inactive GDP form in both wild-type and oncogenic Ras. Here we show by HPLC, mass spectrometry and NMR spectroscopy that the mechanism of this DABP-GTPase reaction is different from the physiological GTPase reaction. The gamma-phosphate group is not attacked by a nucleophilic water molecule, but rather by the aromatic amino group of the analogue, which leads to the generation of a stable cyclic diamidate product. These findings have potential implications for the development of anti-Ras drugs.

Benzophenones↗
PubMed2004

Catechol-O-methyltransferase inhibitors versus active comparators for levodopa-induced complications in Parkinson's disease.

BACKGROUND: As Parkinson's disease progresses the control of the symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to increase the duration of effect of the levodopa dose and thus reduce the time patients spend in the relatively immobile 'off' phase. OBJECTIVES: To compare the efficacy and safety of adjuvant COMT inhibitor therapy versus active comparators in patients with Parkinson's disease, already established on levodopa and suffering from motor complications. SEARCH STRATEGY: Electronic searches of the Cochrane Controlled Trials Register (The Cochrane Library Issue 1, 2003), MEDLINE (1966-2003), EMBASE (1974-2003), were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of COMT inhibitors were contacted. SELECTION CRITERIA: Randomised controlled trials of adjuvant COMT inhibitor therapy versus an active comparator in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of withdrawals and adverse events. MAIN RESULTS: Two trials were found that examined the efficacy of a COMT inhibitor against an active comparator (n = 349). Koller 1998 compared the efficacy of tolcapone versus pergolide (n = 203) over 12 weeks and TSG 1999 compared the efficacy of tolcapone versus bromocriptine (n = 146) over 8 weeks. No trials were found that compared entacapone with active comparators. Tolcapone produced similar benefits to bromocriptine in 'off' time reduction, motor impairment and disability ratings over three months of therapy. Tolcapone produced a greater reduction in levodopa dosage than bromocriptine. Tolcapone produced similar benefits to pergolide in levodopa dose reduction, motor impairment and disability ratings, and in generic health-related quality of life scales over the first two months of therapy. Tolcapone produced a greater improvement in the disease-specific quality of life scale PDQ-39 than pergolide. Nausea, constipation and orthostatic complaints were greater with agonist therapy, but otherwise the frequency of adverse events and withdrawals from treatment were similar with the two classes of adjuvant medication. One patient had significantly elevated liver enzymes whilst on tolcapone, but otherwise the frequency of adverse events and withdrawals from treatment were similar. REVIEWERS' CONCLUSIONS: The two trials comparing tolcapone with the dopamine agonists bromocriptine and pergolide were underpowered to detect clinically relevant differences between them. This is based on medium-term evidence. No evidence was found comparing entacapone with active comparators. Further larger and longer-term trials are required to compare tolcapone with entacapone and COMT inhibitor therapy with alternative adjuvant classes of drug in later Parkinson's disease such as dopamine agonists and monoamine oxidase inhibitors.

Antiparkinson Agents↗
PubMed2004

Catechol-O-methyltransferase inhibitors for levodopa-induced complications in Parkinson's disease.

BACKGROUND: As Parkinson's disease progresses the control of motor symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to increase the duration of effect of each levodopa dose and thus reduce the time patients spend in the relatively immobile 'off' phase. OBJECTIVES: To compare the efficacy and safety of adjuvant COMT inhibitor therapy versus placebo in patients with Parkinson's disease, already established on levodopa and suffering from motor complications. SEARCH STRATEGY: Electronic searches of the Cochrane Controlled Trials Register, (The Cochrane Library Issue 1, 2003), MEDLINE (1966-2003), EMBASE (1974-2003), were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of COMT inhibitors were contacted. SELECTION CRITERIA: Randomised controlled trials of adjuvant COMT inhibitor therapy versus a placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of withdrawals and adverse events. MAIN RESULTS: Fourteen trials fulfilled the inclusion criteria. 2566 patients with Parkinson's disease and motor fluctuations were included in this review. Eight trials examined entacapone versus placebo in a total of 1560 patients. These trials were between two and twelve months in duration. Six trials examined tolcapone versus placebo in a total of 1006 patients. These trials were between six weeks and twelve months in duration. Both tolcapone and entacapone reduced 'off' time, reduced levodopa dose and modestly improved motor impairments and disability. This was at the expense of increased risk of dyskinesias, nausea, vomiting, and diarrhoea. A few participants taking tolcapone were found to have raised liver enzyme levels. REVIEWERS' CONCLUSIONS: In the management of the motor complications seen in Parkinson's disease, tolcapone and entacapone can be used to reduce off time, reduce levodopa dose, and modestly improve motor impairment and disability. This is based on, at best, medium term evidence. However some participants on tolcapone had raised liver enzymes. This combined with three cases of fatal hepatic toxicity found during post-marketing surveillance has raised concerns over the safety of tolcapone.

Antiparkinson Agents↗
PubMed2000

Illness impact and adjustment to Parkinson's disease: before and after treatment with tolcapone.

Research on the impact of disease and treatment on health status and quality of life in patients with movement disorders is limited. We studied quality of life in 46 patients with Parkinson's disease (PD) to determine whether the impact of illness and psychosocial adjustment to illness were improved by 42 days of adjunctive therapy with tolcapone (50 mg, 200 mg, or 400 mg three times a day). This study was conducted in parallel with a double-blind, placebo-controlled, dose-response study of the safety and efficacy of tolcapone in combination with levodopa/carbidopa therapy. Only a subset of individuals from the larger study participated. In the quality of life study, illness impact and adjustment to illness were measured subjectively by the Sickness Impact Profile (SIP) and the Psychosocial Adjustment to Illness Scale-Self-Report (PAIS-SR). Patient ratings of total illness impact (p = 0.003), physical illness impact (p = 0.05), and psychosocial illness impact (p = 0.007) improved significantly in individuals receiving tolcapone compared with those receiving placebo. There was no statistically significant difference in adjustment to illness when the tolcapone and placebo groups were compared; however, 17 of 21 adjustment to illness indicators showed improvement.

Adaptation, Psychological↗
PubMed2004

Non-thiol farnesyltransferase inhibitors: utilization of the near aryl binding site by 5-arylacetylaminobenzophenones.

We recently described two novel aryl binding sites of farnesyltransferase. The arylacetyl residue was designed as an appropriate substituent for our benzo-phenone-based AAX-peptidomimetic compound capable of occupying the near aryl binding site which is located next to the catalytic zinc ion. Non-thiol farnesyl-transferase inhibitors with micromolar to submicromolar activity were obtained.

Alkyl and Aryl Transferases↗
PubMed1994

Application of the radical pair mechanism to free radicals in organized systems: can the effects of 60 Hz be predicted from studies under static fields?

The influence of 60-Hz magnetic fields on free radical reactions can be quantitatively predicted from the knowledge of the effect of static fields on free radical behavior. Studies of radical reactions in micellar systems show that the behavior under a 60-Hz field is identical to that under a static field at any given point in time.

Benzophenones↗
PubMedDate not supplied

Mixed-bed polymeric o-nitrobenzophenone reagents for the on-line derivatization of amines in high performance liquid chromatography.

Several polymer-bound o-nitrobenzophenone reagents containing different detector-sensitive tags have been combined in the same reactor for the on-line derivatization of amine samples. The formation of multiple derivatives allows numerous opportunities for quantitation from the same injection, and also allows improved identification from the retention times of the multiple derivatives. Changing the reaction conditions changes the ratio of the products formed, so that changes in the ratio of peak heights and areas can also be used for analyte identification. In this work, propylamine was derivatized in acetonitrile on-line, precolumn. Changing the reaction conditions, of reaction time, temperature, solvent, presence of catalyst and the components of the reactor, changed the ratio of the derivatives formed. These changes in product formation with changing reaction conditions were applied to the identification and quantitation of amphetamine and methamphetamine in urine. The drugs were identified by the retention times of their derivatives, the ratio of the peak areas of the derivatives and the change in the ratios after changing reaction conditions. Each derivative was also used for quantitation of levels of spiked concentrations of amphetamine and methamphetamine, with relative errors less than 8%.

Amines↗
PubMedDate not supplied

Polymeric reagents for derivatizations in micellar electrokinetic chromatography.

A polymer immobilized o-nitrobenzophenone reagent was prepared for analysis of amine drugs in micellar electrokinetic chromatography (MEKC). A model compound, propylamine, was used to characterize the reagent's performance in MEKC. Derivatizations were performed on the CE instrument with reagent in the sample vial. The yielded derivative was directly sampled from the reaction mixture, and directly injected onto the MEKC system. The derivatization reagent was also applied to the derivatization of n-alkyl amine mixtures and amino acids. The method was validated for adamantanamine in urine and in plasma by single-blind spike analysis. Precisions and accuracies for all samples were less than 6.0% for urine samples and 10% for plasma samples. The procedure was a direct injection technique requiring minimal sample preparation for the analysis of drugs in biofluids.

Amantadine↗
PubMed2004

Evaluation of chiral recognition ability of a novel uranyl-salophen-based receptor: an easy and rapid testing protocol.

A novel member of a new class of chiral uranyl-salophen complexes has been synthesised. The chiral recognition ability of this receptor toward the enantiomers of two primary amines, a sulfoxide, and a quaternary ammonium chloride has been evaluated for the first time. The enantioselectivities obtained are encouraging. The NMR method developed for this purpose allows a fast, quantitative determination of the enantioselectivity of the host directly from its racemic mixture and could find application as a preliminary screening tool in the search for new receptors using combinatorial methods. The experiments carried out in this context demonstrated also that the activation barrier for the racemisation of such chiral uranyl-salophen receptors is much higher than the lower limit of 21 kcal mol(-1) previously reported.

Benzophenones↗
PubMed2005

Internal electrolyte temperatures for polymer and fused-silica capillaries used in capillary electrophoresis.

Polymers are important as materials for manufacturing microfluidic devices for electrodriven separations, in which Joule heating is an unavoidable phenomenon. Heating effects were investigated in polymer capillaries using a CE setup. This study is the first step toward the longer-term objective of the study of heating effects occurring in polymeric microfluidic devices. The thermal conductivity of polymers is much smaller than that of fused silica (FS), resulting in less efficient dissipation of heat in polymeric capillaries. This study used conductance measurements as a temperature probe to determine the mean electrolyte temperatures in CE capillaries of different materials. Values for mean electrolyte temperatures in capillaries made of New Generation FluoroPolymer (NGFP), poly-(methylmethacrylate) (PMMA), and poly(ether ether ketone) (PEEK) capillaries were compared with those obtained for FS capillaries. Extrapolation of plots of conductance versus power per unit length (P/L) to zero power was used to obtain conductance values free of Joule heating effects. The ratio of the measured conductance values at different power levels to the conductance at zero power was used to determine the mean temperature of the electrolyte. For each type of capillary material, it was found that the average increase in the mean temperature of the electrolyte (DeltaT(Mean)) was directly proportional to P/L and inversely proportional to the thermal conductivity (lambda) of the capillary material. At 7.5 W/m, values for DeltaT(Mean) for NGFP, PMMA, and PEEK were determined to be 36.6, 33.8, and 30.7 degrees C, respectively. Under identical conditions, DeltaT(Mean) for FS capillaries was 20.4 degrees C.

Benzophenones↗
PubMed2007

Effects of a catechol-O-methyltransferase inhibitor on catechol estrogen-induced cellular transformation, chromosome aberrations and apoptosis in Syrian hamster embryo cells.

To examine a possible mechanism of endogenous estrogen-induced carcinogenesis, we studied the effect of the catechol-O-methyltransferase (COMT) inhibitor Ro 41-0960 on cell transforming and clastogenic activities of 2 catechol estrogens 2- and 4-hydroxyestrone (2- or 4-OHE1) using Syrian hamster embryo (SHE) cells. COMT activity was assayed by determining the methylation of 2- or 4-OHE1 using gas chromatography. The production of 2-methoxyestrone in cultures treated with 2-OHE1 was approximately 2-fold that of 4-methoxyestrone in cultures treated with 4-OHE1. 4-OHE1 induced morphological transformation at a higher frequency than 2-OHE1 did and the frequencies of cell transformation and chromosome aberrations were not significantly changed in cells treated with 4-OHE1 in the presence of Ro 41-0960. In contrast, the frequencies of cell transformation and chromosome aberrations were markedly increased in cells treated with 2-OHE1 along with Ro 41-0960 when compared to cells treated with 2-OHE1 alone. In addition, both catechol estrogens induced P53 protein expression and apoptosis. The frequencies of apoptotic cells induced by the catechol estrogens were modified by the COMT inhibition in a manner similar to those observed with the chromosome aberrations assay and the cell transformation assay, indicating that each effect by the catechol estrogens at the three measured endpoints might be caused by a mechanism similar to the others. Our findings indicate that COMT activity has an influence on cell transforming activity and its related genetic effects of catechol estrogens in SHE cells, which implies that an individual activity of COMT may be one of the etiological factors in endogenous estrogen-induced carcinogenesis.

Animals↗
PubMed1997

Evaluation of pharmacokinetic interaction between bromfenac and phenytoin in healthy males.

An open-label, nonrandomized, multiple-dose, inpatient study was conducted in healthy male volunteers to compare the pharmacokinetics of bromfenac and phenytoin when the drugs are given individually and concomitantly. Twelve men received multiple oral doses of bromfenac for 4 days and then oral phenytoin for up to 14 days followed by concomitant administration of bromfenac and phenytoin for 8 days. Concomitant administration of the two drugs caused an approximate 40% decrease in the mean peak plasma concentration (Cmax) and the interdose area under the concentration-time curve (AUC) of bromfenac. The oral clearance (Clpo) of bromfenac doubled and the volume of distribution increased by 77%. For phenytoin, the mean peak serum concentration and the AUC increased by 9% and 11%, respectively, in the presence of bromfenac. The only change in unbound phenytoin was a 16% increase in the AUC. Although statistically significant, the changes in the pharmacokinetic parameters of phenytoin and unbound phenytoin were small. Adjustments in the dose of phenytoin should not be required during concomitant administration of bromfenac, although each patient's clinical status should be evaluated individually.

Adult↗
PubMed1998

Double-blind, single-dose comparison of bromfenac sodium, tramadol, and placebo after oral surgery.

This double-blind, parallel-group study was performed at a single site in patients with moderate or severe pain after oral surgery to remove one or more impacted third molars. Patients recorded their pain intensity at baseline and were then assigned to receive a single dose of bromfenac sodium (25 mg or 50 mg), tramadol (100 mg), or placebo, using a randomized double-blind code. At regular intervals for up to 8 hours after study drug administration, pain intensity and pain relief were recorded and were used to derive the efficacy variables, total pain relief (TOTPAR), pain intensity difference (PID), and summed pain intensity difference (SPID). Both doses of bromfenac were superior to tramadol and placebo in terms of hourly and peak pain relief and PID. The 3-hour and 8-hour TOTPAR and SPID results for both doses of bromfenac also were significantly superior to those for tramadol and placebo, whereas the scores for tramadol did not show superiority to placebo. Similarly, both doses of bromfenac were superior to tramadol and placebo as measured by patient global assessment, time to meaningful pain relief, and duration of pain relief. Bromfenac was well tolerated and was equivalent to placebo with respect to treatment-emergent study events. Overall, significantly more study events (total), digestive events (particularly nausea and vomiting), and nervous system events (particularly dizziness) occurred in patients treated with tramadol than in those in other treatment groups. Single oral doses of bromfenac were more effective, longer-acting, and better tolerated than single doses of tramadol in providing pain relief after oral surgery.

Adolescent↗
PubMed1998

Metabolic disposition of 14C-bromfenac in healthy male volunteers.

The metabolic disposition of 14C-bromfenac, an orally active, potent, nonsteroidal, nonnarcotic, analgesic agent was investigated in six healthy male subjects after a single oral 50-mg dose. The absorption of radioactivity was rapid, producing a mean maximum plasma concentration (Cmax) of 4.9 +/- 1.8 microg x equiv/mL, which was reached 1.0 +/- 0.5 hours after administration. Unchanged drug was the major component found in plasma, and no major metabolites were detected in the plasma. Total radioactivity recovered over a 4-day period from four of the six subjects averaged 82.5% and 13.2% of the dose in the urine and feces, respectively. Excretion into urine was rapid; most of the radioactivity was excreted during the first 8 hours. Five radioactive chromatographic peaks, a cyclic amide and four polar metabolites, were detected in 0- to 24-hour urine samples. Similarity of metabolite profiles between humans and cynomolgus monkeys permitted use of this animal model to generate samples after a high dose for structure elucidation. Liquid chromatography/mass spectrometry (LC/MS) analysis of monkey urine samples indicated that the four polar metabolites were two pairs of diastereoisomeric glucuronides whose molecular weight differed by two daltons. Enzyme hydrolysis, cochromatography, and LC/MS experiments resulted in the identification of a hydroxylated cyclic amide as one of the aglycones, which formed a pair of diastereoisomeric glucuronides after conjugation. Data also suggested that a dihydroxycyclic amide formed by the reduction of the ketone group that joins the phenyl rings formed the second pair of diastereoisomeric glucuronides. Further, incubation of various reference standards in control (blank) urine and buffer with and without creatinine indicated that the hydroxy cyclic amide released from enzyme hydrolysis can undergo ex vivo transformations to a condensation product between creatinine and an alpha-keto acid derivative of the hydroxy cyclic amide that is formed by oxidation and ring opening. Further experiments with a dihydroxylated cyclic amide after reduction of the keto function indicated that it too can form a creatinine conjugate.

Adolescent↗