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Weak Inhibition (weak + inhibition)
Selected AbstractsBarley polyamine oxidase: characterisation and analysis of the cofactor and the N-terminal amino acid sequencePHYTOCHEMICAL ANALYSIS, Issue 3 2001Anna Radová Abstract This paper reports the first purification method developed for the isolation of an homogeneous polyamine oxidase (PAO) from etiolated barley seedlings. The crude enzyme preparation was obtained after initial precipitation of the extract with protamine sulphate and ammonium sulphate. The enzyme was further purified to a final homogeneity (by the criteria of isoelectric focusing and SDS,PAGE) using techniques of low pressure chromatography followed by two FPLC steps. The purified yellow enzyme showed visible absorption maxima of a flavoprotein at 380 and 450,nm: the presence of FAD as the cofactor was further confirmed by measuring the fluorescence spectra. Barley PAO is an acidic protein (pI 5.4) containing 3% of neutral sugars: its molecular mass determined by SDS,PAGE was 56,kDa, whilst gel permeation chromatography revealed the higher value of 76 kDa. The N-terminal amino acid sequence of barley PAO shows a high degree of similarity to that of maize PAO and to several other flavoprotein oxidases. The polyamines spermine and spermidine were the only two substrates of the enzyme with Km values 4,×,10,5 and 3,×,10,5,M and pH optima of 5.0 and 6.0, respectively. Barley polyamine oxidase is markedly inhibited by acridine dyes and hydrazines. Weak inhibition was observed with substrate analogues, aminoaldehydes, metal chelating agents and several other compounds. Copyright © 2001 John Wiley & Sons, Ltd. [source] The New Metabolite (S)-Cinnamoylphosphoramide from Streptomyces sp. and Its Total SynthesisEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 30 2008Melanie Quitschau Abstract The tunicate-associated strain Streptomyces sp. JP90 produces the unprecedented metabolite cinnamoylphosphoramide (1) among several other compounds. Structure elucidation was accomplished by NMR spectroscopic studies and efficient total synthesis. The absolute configuration at phosphorus was determined by synthesis of both enantiomers of 1 performing a resolution of the corresponding diastereomeric phosphoramides of L -phenylalanine ethyl ester. Unusual cinnamic acid derivative 1 represents the first bacterial organophosphoramide. As it matches the Schrader's formula for insecticidal organophosphates, its biological activity was investigated. A weak inhibition of acetylcholinesterase was observed in in vitro tests, and water-soluble analogues of 1 were prepared. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Effects of glycyrrhetinic acid derivatives on hepatic and renal 11,-hydroxysteroid dehydrogenase activities in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2003Yoshihito Shimoyama The purpose of this study was to examine the structure and activity relationships of glycyrrhetinic acid derivatives on the inhibition of hepatic and renal 11,-hydroxysteroid dehydrogenases (HSDs) in rats. Furthermore, we explored whether inflammatory effect of the derivatives is involved in the inhibition of 11,-HSD activity. 18,-Glycyrrhetinic acid (Ia) potently inhibited 11,-HSD activity of hepatic (IC50 (concentration giving 50% inhibition of cortisone production) = 0.09 ,m) and renal (IC50 = 0.36 ,m) homogenate. The inhibitory effect of 18,-glycyrrhetol (Id) modified at the 30-position of glycyrrhetinic acid was weaker than that of glycyrrhetinic acid itself. 18,-24-Hydroxyglycyrrhetinic acid (Ie), oxidized at the 24-position, remarkably reduced the inhibitory activity for both enzymes. 18,-11-Deoxoglycyrrhetinic acid (IIc) showed the same inhibitory effect as glycyrrhetinic acid on hepatic 11,-HSD activity, but less effect on renal 11,-HSD activity. Furthermore, the inhibitory activity of 18,-deoxoglycyrrhetol (IIa), modified at the 11- and 30-position, was markedly decreased. Dihemiphthalate derivatives (IIb, IIIb and IVb) of deoxoglycyrrhetol (IIa), 18,-olean-9(11), 12-diene-3,, 30-diol (IIIa) and olean-11, 13(18)-diene-3,, 30-diol (IVa), which are anti-inflammatory agents, also showed weak inhibition against both hepatic and renal 11,-HSDs. While glycyrrhetinic acid (200 mg kg,1, p.o.) significantly inhibited 11,-HSD activity in rat liver and kidney at 3 h after administration, compound IVb (100 mg kg,1, p.o.) had no effect on either enzyme activity. In addition, the circulating corticosterone level was slightly increased by glycyrrhetinic acid but not by compound IVb. These results suggest that the anti-inflammatory effects of compound IVb, derived from glycyrrhetinic acid, are not due to accumulation of steroids induced by the inhibition of 11,-HSD activity. Our data also showed that the 11-, 24- and 30-positions of glycyrrhetinic acid may play important roles in the differential inhibitory effects on 11,-HSD isozyme activity. [source] Distribution and characterization of hemolytic activity by an oral anaerobe from the Streptococcus milleri groupMOLECULAR ORAL MICROBIOLOGY, Issue 2 2004T. Yamaguchi Some oral anaerobes from the Streptococcus milleri strain group were found to secrete human specific hemolytic toxin, which was detected when bacteria were cultured in Todd-Hewitt broth and Brain Heart Infusion broth. The toxin elicited by the Streptococcus intermedius strain was partially fractionated by ammonium sulfate precipitation. Preincubation with glutathione or cysteine showed significant inhibiting effects; however, no effects were seen with dithiothreitol or ,-mercaptoethanol, and cholesterol was a weak inhibitor. Five kinds of protease inhibitor had no effect on the hemolytic activity, and rabbit preimmune and immune sera against the bacterial cells showed weak inhibition at a similar level. Digestion with trypsin, chymotrypsin, proteinase-K, subtilisin and pronase-P brought about a rise in activity, followed by a decrease during long-term incubation. Other enzymes tested showed no effects. Further, the presence of the intermedilysin gene in the portion with hemolytic activity was not identified by polymerase chain reaction. [source] Firing properties and functional connectivity of substantia nigra pars compacta neurones recorded with a multi-electrode array in vitroTHE JOURNAL OF PHYSIOLOGY, Issue 10 2010Nicola Berretta Dopamine (DA) neurones of the substantia nigra pars compacta (SNc) are involved in a wide variety of functions, including motor control and reward-based learning. In order to gain new insights into the firing properties of neuronal ensembles in the SNc, we recorded extracellular single units from spontaneously active neurones, using a multi-electrode array (MEA) device in midbrain slices. The majority of neurones (50.21%) had a low firing frequency (1,3 Hz) and a stable pacemaker-like pattern, while others (44.84%) were irregular, but still firing at a low rate. The remaining population (4.95%) comprised neurones with a regular higher firing rate (5,10 Hz). High rate neurones, on the whole, were insensitive to DA (30 ,m), while low rate neurones were mostly inhibited by DA, although responding either with a prominent or a weak inhibition. However, we recorded low rate regular neurones that were insensitive to DA, or irregular low rate neurones excited by DA. Interestingly, we found pairs of active neurones (12.10 ± 3.14%) with a significant proportion of spikes occurring synchronously. Moreover, the crosscorrelation probability in each pair tended to increase in response to DA. In conclusion, MEA recordings in midbrain slices reveal a much more complex picture than previously reported with regard to the firing pattern and DA sensitivity of spontaneously active SNc neurones. Moreover, the study opens new prospectives for the in vitro investigation of functional connectivity in the midbrain dopaminergic system, thus proposing new targets for the pharmacological treatment of DA-dependent neurological disorders. [source] Effect of zolpidem on human Cytochrome P450 activity, and on transport mediated by P-glycoproteinBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 9 2002Lisa L. von Moltke Abstract The influence of high concentrations of zolpidem (100 ,M, corresponding to approximately 200 times maximum therapeutic concentrations) on the activity of six human Cytochrome P450 (CYP) enzymes was evaluated in a model system using human liver microsomes. Zolpidem produced negligible or weak inhibition of human CYP1A2, 2B6, 2C9, 2C19, 2D6, and 3A. Transport of rhodamine 123, presumed to be mediated mainly by the energy-dependent efflux transport protein P-glycoprotein, was studied in a cell culture system using a human intestinal cell line. High concentrations of zolpidem (100 ,M), exceeding the usual therapeutic range by more than 100-fold, produced only modest impairment of rhodamine 123 transport. The findings indicate that zolpidem is very unlikely to cause clinical drug interactions attributable to impairment of CYP activity or P-gp mediated transport. Copyright © 2002 John Wiley & Sons, Ltd. [source] | |||||||||||||