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At least 73 records · Page 4Linked to original sources
PubMed1990

Effects of DM-9384, a pyrrolidone derivative, on alcohol- and chlordiazepoxide-induced amnesia in mice.

The effects of N-(2,6-dimethyl-phenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide (DM-9384), a new pyrrolidone derivative, were investigated on ethanol- and chlordiazepoxide (CDP)-induced amnesia animal model using the passive avoidance task in comparison with aniracetam, another pyrrolidone derivative. Pretraining administration of DM-9384 attenuated ethanol- and CDP-induced amnesia, whereas aniracetam failed to do so. The effects of DM-9384 on CDP-induced amnesia were antagonized by bicuculline, a GABAA receptor antagonist, but not by scopolamine, a muscarinic acetylcholine receptor antagonist and flumazenil, a benzodiazepine receptor antagonist. These results suggest that DM-9384 attenuates CDP-induced amnesia by interacting with the GABAergic neuronal system.

Amnesia↗
PubMed1995

Isolation and characterization of pcp, a gene encoding a pyrrolidone carboxyl peptidase in Staphylococcus aureus.

The pcp gene, encoding a pyrrolidone carboxyl peptidase (PYRase), was cloned from a lambda GT11 genomic library prepared from Staphylococcus aureus FDA 574 and sequenced. The pcp gene is located 740 bp downstream from cna, a gene that encodes a collagen-binding adhesin in S. aureus. S. aureus pcp encodes a 212-amino-acid (aa) polypeptide. The pcp gene was overexpressed in Escherichia coli and the PYRase purified to homogeneity. The recombinant enzyme exhibited biological activity, as determined using the chromogenic substrate L-pyroglutamyl-beta-napthylamide. Biochemical analysis of the PYRase using thiol-blocking chemicals suggested that the enzyme belongs to the cysteine peptidase family. Moreover, multiple sequence alignment revealed a high degree of similarity to previously described bacterial PYRases. This family of peptidases has been used to selectively remove the N-terminal pyrrolidone carboxylic acid residue found on certain blocked proteins and peptides prior to aa sequencing. However, the exact biological role of PYRases has yet to be elucidated.

Amino Acid Sequence↗
PubMed2006

Cytocompatibility of poly(acrylonitrile-co-N-vinyl-2-pyrrolidone) membranes with human endothelial cells and macrophages.

Polyacrylonitrile modified with N-vinyl-2-pyrrolidone (NVP) shows good hemocompatibility. This work, which aims to evaluate the cytocompatibility of membranes fabricated from poly(acrylonitrile-co-N-vinyl-2-pyrrolidone) (PANCNVP), studied the adhesion of macrophages and endothelial cell (EC) cultures. It was found that PANCNVP membranes with higher NVP content decreased the adhesion of both macrophages and ECs. Compared with polyacrylonitrile and tissue culture polystyrene control, however, these PANCNVP membranes promoted the proliferation of ECs. Furthermore, the viability of ECs cultured on the PANCNVP membrane surfaces was also relatively competitive. Both static and dynamic water contact angle measurements were conducted to explain the nature of cell adhesion to the PANCNVP membranes. On the basis of these results and the phenomena of water swelling and water states reported previously, it was presumed that the coexistence of large amounts of bound water and free water induced by NVP moieties are responsible for the lower adhesion and better function of cells adhering to the PANCNVP membranes.

Acrylic Resins↗
PubMed2004

Discovery of potent pyrrolidone-based HIV-1 protease inhibitors with enhanced drug-like properties.

We have developed efficient syntheses of the HIV-1 protease inhibitor 4 and its analogues, which incorporate the pyrrolidone scaffold 2 as P1-P2 moiety. Evaluation of these analogues in the HIV-1 protease enzyme assay resulted in discovery of potent and more water soluble meta-amino- and meta-hydroxy inhibitors 17b and 19b. The SAR observed in this class of PIs could be rationalized with aid of the X-ray structure of inhibitor 28 co-crystallized with the HIV-1 protease, which suggested that the polar meta- (but not para-) benzyl substituents in P2 could side-step the hydrophobic S2 enzyme active pocket by rotating the P2 moiety around its Cbeta-Cgamma bond. Such reorientation allows to engage the unsubstituted, hydrophobic edge of benzyl moiety in P2 in the requisite P2/S2 hydrophobic interaction, and projects polar meta-substituent into the bound water. It appears that the meta-position can be chemically derivatized without potency loss of thus resulting inhibitors, as evidenced by potent 22-26. We thus identified pyrrolidone 2-based inhibitors exemplified by 17b and 19b, which uniquely accommodate both high enzyme potency and which provide a platform for fine-tuning of drug-like properties in this class of PIs by additional chemical manipulations on the meta-position.

Drug Design↗
PubMed2005

Poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide)-g-poly(vinyl pyrrolidone): synthesis and characterization.

Pluronic poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO) block copolymers are grafted with poly(vinyl pyrrolidone) by free radical polymerization of vinyl pyrrolidone with simultaneous chain transfer to the Pluronic in dioxane. This modified polymer has both thermal responsiveness and remarkable capacity to interact with a wide variety of hydrophilic and hydrophobic pharmaceutical agents which is very attractive for medical applications. The chemical structure of the graft copolymers was characterized by FTIR and 1H NMR spectroscopy. Polymerization conditions such as initiators, feed ratio, and reaction times are studied to obtain the ideal graft copolymer.

Journal Article↗
PubMed2006

Levels of N-methyl-2-pyrrolidone (NMP) and its metabolites in plasma and urine from volunteers after experimental exposure to NMP in dry and humid air.

The aim of this study was to investigate if the uptake of N-methyl-2-pyrrolidone (NMP), a widely used industrial chemical, increases after exposure to NMP in humid air compared to dry air. NMP has been described to be an airway irritant and a developmentally toxic compound. Six male volunteers were exposed to NMP, three at the time, for 8h in an exposure chamber. They were each exposed on four different occasions to air levels of 0 and 20mg NMP/m(3) in dry and humid air. Blood and urine were sampled before, during and up to 5 days after the end of the 8-h exposure. Plasma and urine were analysed for NMP and its metabolites, using liquid chromatography-tandem mass spectrometry. There was no statistically significant increase in the total cumulated excretion of NMP and its metabolites in urine after exposure in humid air as compared to dry air. Furthermore, there were no differences in the levels of peak concentrations in either plasma or urine. Also, no differences were found in AUC between the exposures. However, there were large individual differences, especially for the exposure in humid air. A not previously identified metabolite in human, 2-pyrrolidone (2-P), was identified. The results do not support a significantly higher absorption of NMP at exposure in humid air as compared to dry air. However, the large individual differences support the use of biological monitoring for assessment of NMP exposure. In addition, 2-P was confirmed to be an NMP metabolite in humans. This may be of importance for the developmental toxicity of NMP since 2-P have been described to be a reproductively toxic substance.

Adult↗
PubMed2002

Dermal exposure to aqueous solutions of N-methyl pyrrolidone.

N-methyl pyrrolidone (NMP) is a substance widely used for its strong and selective solvent capacity. The strong potential NMP has for skin absorption makes biological monitoring ideal for exposure assessment. This study looked at brief exposures to NMP in aqueous solutions over a range of concentrations. Two volunteers placed one hand in NMP solutions ranging from 5 to 25% for as long as 15 min followed by urine collection for 48 h. The analyte of interest (analysed by GC-MS) was the NMP metabolite 5-hydroxy-N-methyl pyrrolidone (5-HNMP). Excretion of 5-HNMP was plotted against time and this showed that urine concentrations were at a maximum after about 10 h and 5-HNMP excretion continued for 48 h after exposure. The half-life of excretion was found to be approximately 11 h. The mean correlation between exposure (as a measure of exposure duration and solution concentration) and total 5-HNMP excreted was 0.9297.

Administration, Cutaneous↗
PubMed2001

Determination of 5-hydroxy-N-methyl-2-pyrrolidone and 2-hydroxy-N-methylsuccinimide in human plasma and urine using liquid chromatography-electrospray tandem mass spectrometry.

A method for simultaneous determination of 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) was developed. These compounds are metabolites from N-methyl-2-pyrrolidone (NMP), a powerful and widely used organic solvent. 5-HNMP and 2-HMSI were purified from plasma and urine by solid-phase extraction using Isolute ENV+ columns, and analysed by liquid chromatography coupled to a mass spectrometer fitted with an atmospheric pressure turbo ion spray ionisation interface in the positive ion mode. The method was validated for plasma and urine concentrations from 0.12 to 25 microg/ml. The recoveries for 5-HNMP and 2-HMSI in plasma were 99 and 98%, respectively, and in urine 111 and 106%, respectively. For 5-HNMP and 2-HMSI, the within-day precision in plasma was 1-4 and 3-6%, respectively, and in urine 2-12 and 3-10%, respectively. The corresponding data for the between-day precision was 5 and 3-6%, respectively, and 4-6 and 7-8%, respectively. The detection limit for 5-HNMP was 4 ng/ml in plasma and 120 ng/ml in urine. For 2-HMSI, it was 5 ng/ml in plasma and 85 ng/ml in urine. The method is applicable for analysis of plasma and urine samples from workers exposed to NMP.

Calibration↗
PubMed2002

Novel spirocyclic pyrrolidones as P2/P1 mimetics in potent inhibitors of HIV-1 protease.

We have developed concise and efficient syntheses of novel spirocyclic pyrrolidones 1-3, which involve the alkylation of pyrrolidone precursor 13 with 1,5-dibromopentane, 16 and 15, followed by an in situ lactamization. Conjugates of 1 and 2 with P1'/P2' hydroxy-indanolamine moiety resulted in novel and potent inhibitors of HIV-1 protease 25 and 26, suggesting that 1 and 2 are novel P2/P1 HIV-PI mimetics.

Alkylation↗
PubMedDate not supplied

Depth profile of free volume in a mixture and copolymers of poly(N-vinyl-pyrrolidone) and poly(ethylene glycol) studied by positron annihilation spectroscopy.

Effect of hydrogen bonding on the depth profile of the free-volume in a mixture (weight ratio of 65:35) of poly(N-vinyl-pyrrolidone) (PVP) and poly(ethylene glycol) (PEG) and the copolymers of vinyl pyrrolidone with poly(ethylene glycol) diacrylate (PVP-PEGDA) and monomethacrylate (PVP-PEGMMA) was studied using positron annihilation spectroscopy. Doppler broadening energy spectra of annihilation radiation and positron annihilation lifetime were measured as a function of positron incident energy (0-30 keV). Significant variations of the free-volume depth profile in terms of the S parameter, ortho-positronium lifetime, intensity, and lifetime distribution are observed as a result of the hydrogen-bonding replacement of covalent bonds. The polymer mixture with hydrogen bonding through two sides of PEG short chains has a larger free volume and a wider distribution than the comb-structured PVP-PEGMMA and the network structured PVP-PEGDA. A longer ortho-positronium lifetime is observed near the surface than in the bulk. This is interpreted in terms of surface effect, free volume, and hydrogen bonding for drug delivery applications of polymeric materials.

Drug Carriers↗
PubMed1996

Fluorescent probe studies of the interactions of 1-alkyl-2-pyrrolidones with stratum corneum lipid liposomes.

Previously, the effects of a series of 1-alkyl-2-pyrrolidones (APs; C2-C8) on the lipoidal pathway of hairless mouse skin (HMS) were studied with a parallel pathway skin model. At their isoenhancement concentrations, these 1-alkyl-2-pyrrolidones induce the same transport enhancement (isoenhancement factor, EHMS) on the lipoidal pathway of the stratum comeum for the probe permeants studied. In the present study, the fluidizing effects of APs upon the stratum comeum lipid liposome (SCLL) bilayer were investigated under these isoenhancement conditions using steady state anisotropy and fluorescence lifetime studies with fluorescent probes 2-, 6-, and 9-(9-anthroyloxy)stearic acids, 16-(9-anthroyloxy)palmitic acid, and 1,6-diphenyl-1,3,5-hexatriene to examine a possible correlation between the fluidizing properties of APs and their enhancement effects on transdermal drug transport. Time-resolved fluorescence decay studies were also conducted to further investigate the fluidizing properties of APs and add support to the steady-state fluorescence results. Under an isoenhancement condition of EHMS = 10, these APs fluidized the alkyl chains of the lipids at intermediate depths (C6-C9) in the SCLL bilayer (a 40-50% decrease in the rotational correlation times) but did not significantly change the fluidity in the deep hydrophobic region of the bilayer. Three rotational correlation times were deduced from the global simultaneous analysis in time-resolved fluorescence decay measurements. The slowest of these (greater than 1000 ns) was attributed to the global motion of SCLLs and is probably related to the static component of steady-state anisotropy. The other two rotational correlation times (on the order of nanoseconds) were in the range expected for the local motion of the fluorophores and may correspond to their vibrational and rotational motions. When the concentrations of APs were increased (increasing the EHMS value), the static component (alpha) decreased. This suggests that APs might induce a general fluidizing effect upon the lipid bilayer (i.e., a decrease in the order of the lipid bilayer). The decrease in the longer rotational correlation time (on the order of nanoseconds) with increasing EHMS value, on the other hand, indicates a possible increase in the "cavity volume" for the hindered motions of the fluorophores (i.e., an increase in the free volume at intermediate depths in the bilayer).

Animals↗
PubMed2001

Acute poisoning with the neonicotinoid insecticide imidacloprid in N-methyl pyrrolidone.

BACKGROUND: Imidacloprid [1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine, CAS 138261-41-3] belongs to a relatively new class of insecticidal chemistry, the chloronicotinyl neonicotinoid compounds. Animal studies indicate relatively low toxicity to mammals because they have resistant nicotinic receptor subtypes compared to insects, as well as protection of the central nervous system by the blood brain barrier. Despite wide usage, human exposure experience resulting in toxicity is quite limited. CASE REPORT: Here, we report a case of acute ingestion of an insecticide formulation containing 9.7% imidacloprid, <2 % surfactant, and the balance as solvent, N-methyl pyrrolidone. Clinical manifestation included drowsiness, disorientation, dizziness, oral and gastroesophageal erosions, hemorrhagic gastritis, productive cough, fever, leukocytosis, and hyperglycemia. The patient recovered without complication with supportive treatment and was discharged 4 days after ingestion. Follow-up barium upper gastrointestinal examination 1 month later was normal. Because moderate to high dose imidacloprid in animals causes central nervous system activation similar to nicotine, including tremors, impaired pupillary function, and hypothermia, it is unclear whether imidacloprid had a causal role in the patient's initial drowsiness and dizziness. It is more likely that the formulation ingredients, particularly N-methyl pyrrolidone, caused most of the clinical symptoms including minor central nervous system depression, gastrointestinal irritation, and hyperglycemia.

Blood Cell Count↗
PubMed2001

X-ray crystalline structures of pyrrolidone carboxyl peptidase from a hyperthermophile, Pyrococcus furiosus, and its cys-free mutant.

In order to elucidate the mechanism of the thermostability of proteins from hyperthermophiles, X-ray crystalline structures of pyrrolidone carboxyl peptidase from a hyperthermophile, Pyrococcus furiosus (PfPCP), and its mutant protein with Ser substituted at Cys142 and Cys188 were determined at 2.2 and 2.7 A resolution, respectively. The obtained structures were compared with those previously reported for pyrrolidone carboxyl peptidases from a hyperthermophilie, Thermococcus litoralis (TlPCP), and from a mesophile, Bacillus amyloliquefaciens (BaPCP). The PfPCP structure is a tetramer of four identical subunits similar to that of the TlPCP and BaPCP. The largest structural changes among the three PCPs were detected in the C-terminal protrusion, which interacts with that of another subunit. A comparison of the three structures indicated that the high stability of PfPCP is caused by increases in hydrophobic interactions and hydrogen bonds, the formation of an intersubunit ion-pair network, and improvement to an ideal conformation. On the basis of the structures of the three proteins, it can be concluded that PfPCP does not have any special factors responsible for its extremely high stability and that the conformational structure of PfPCP is superior in its combination of positive and negative stabilizing factors compared with BaPCP.

Amino Acid Sequence↗
PubMed1996

Stillbirth after occupational exposure to N-methyl-2-pyrrolidone. A case report and review of the literature.

N-methyl-2-pyrrolidone is a solvent that is increasingly used in a variety of industries, including petroleum refining, microelectronics, pesticide formulation, and veterinary medicine. Animal studies have demonstrated fetotoxic effects after maternal exposure to doses that have minimal to no adverse effect on the mothers. The fetotoxicity comprises resorption, stillbirth, and low birthweight and delayed ossification in surviving young. We report a human case of intrauterine growth retardation followed by fetal demise at 31 weeks gestation. The mother was a laboratory worker with no other apparent risk factors, who sustained occupational exposure to N-methyl-2-pyrrolidone throughout the first trimester of pregnancy. Laboratory work and solvent exposure have both previously been associated with adverse reproductive outcomes. Laboratories and other industries that use suspected reproductive toxins should have reproductive health policies in place that allow for decision-making based on toxicologic review, exposure assessment, and medical evaluation. These policies should allow for voluntary removal of prospective parents until environmental assessment and controls are instituted.

Adult↗
PubMed1980

Ultrastructural effects of the high molecular weight cryoprotectants Dextran and polyvinyl pyrrolidone on liver and brown adipose tissue in vitro.

The ultrastructural changes caused by incubation of rat liver and brown fat in buffered solutions of high molecular weight cryoprotectives (Dextran and polyvinyl pyrrolidone) at high concentrations (up to 25% w/v) have been examined. Under appropriate conditions of incubation rather small qualitative changes were found. Hepatocytes showed some signs of plasmolysis. Evidence for the endocytosis of Dextran and polyvinyl pyrrolidone was obtained. Cryoultramicrotomy of unfixed, quench-frozen specimens after the same incubation procedures showed good cutting properties and only slight ice-crystal damage. Several of the larger tissue compartments were recognizable in such sections. Although high molecular weight cryoprotectants do penetrate cells by endocytosis (and these effects require further functional evaluation), the present observations provide further support for the idea that such compounds significantly improve the quench-freezing of biological specimens and offer a practical way forward for the preparation of material for X-ray microanalysis of diffusible elements.

Adipose Tissue, Brown↗
PubMed1993

Removal of N-terminal formyl groups and deblocking of pyrrolidone carboxylic acid of proteins with anhydrous hydrazine vapor.

Many proteins have a blocked alpha-amino group which renders them inaccessible to sequence analysis by the classical Edman degradation procedure. Blockage typically occurs when the alpha-amino groups are acylated with acetyl or formyl groups or when the N-terminal residue is pyrrolidone carboxylic acid formed by cyclization of glutamine. We have found that N-formyl groups of proteins and peptides can be removed by exposure to hydrazine vapor at -5 degrees C for 8 h. Under these conditions, peptide-bond cleavage or modification of the constituent amino-acid residues does not occur. Deblocking of N-terminal pyrrolidone carboxylate residues by conversion to gamma-hydrazidyl glutamic acid can be achieved by exposure to hydrazine vapor at 20 degrees C for 4 h. These conditions cause partial modification of asparagine and glutamine residues to their corresponding hydrazides, and conversion of arginine residues to ornithine.

Amino Acid Sequence↗
PubMed1990

Enhancing effect of combining two pyrrolidone vehicles on transdermal drug delivery.

The enhancing effect of combining 1-methyl-2-pyrrolidone (MP) and 1-lauryl-2-pyrrolidone (LP) as the vehicles for transdermal penetration of phenolsulphonphthalein (phenol red) has been investigated by using an in-vitro technique with excised rat skin. LP had a higher enhancing effect on the penetration of phenol red than MP, but there was a long lag time before steady-state penetration was attained. A potent effect with a shorter lag time was obtained when MP and LP were used together. This potentiation was maintained when the concentration of MP was decreased by 95%. The combined vehicle also enhanced the skin accumulation of phenol red. MP promoted the rapid penetration of LP into the skin and potentiated the enhancing effect of LP on the penetration of phenol red and thereby shortened the lag time. The combined vehicle also enhanced the penetration of the hydrophilic anticancer agent, 5-fluorouracil.

Administration, Cutaneous↗
PubMed2006

Cell growth on tissue-engineering scaffolds prepared by gamma irradiation grafting of N-vinyl-2-pyrrolidone onto polyvinyl alcohol.

In the field of tissue engineering, promoting cell attachment and proliferation in polymer matrices is an attractive challenge for treating patients suffering from the loss or dysfunction of tissues or organs. In this study we have investigated the effect of grafting N-vinyl-2-pyrrolidone (NVP) by gamma irradiation onto polyvinyl alcohol (PVA), a highly hydrophilic and non-toxic material. PVA scaffolds were prepared by freeze-thaw and progen (glycerol) methods. In the first method, samples were freeze-thawed for three consecutive cycles at -25 degrees C (90 min) and room temperature (60 min); in the latter, 0-40% glycerol was used as progen. Gamma irradiation of the scaffolds in the presence of NVP was performed at different concentrations (2, 3, 4 and 6%) with 5, 10 and 15 kGy 60Co. The highest percentage of grafting was obtained at 4% NVP solution and 15 kGy. Cell attachment was optimal for the scaffolds prepared using freeze-thaw and glycerol methods with 3.8% and 2.7% polyvinyl pyrrolidone (PVP), respectively.

Animals↗