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At least 865 records · Page 48Linked to original sources
PubMed1975

On the role of tryptophan residues in the mechanism of action of glyceraldehyde-3phosphate dehydrogenase as tested by specific modification.

A method is described to selectively modify one of the three tryptophan residues of the subunit of glyceraldehyde-3-phosphate dehydrogenase from yeast. As modifying agent dimethyl (2-hydroxy-5-nitrobenzyl) sulfonium bromide was used. The residue which is modified by the procedure described has been identified as Trp-193. There are either one or two molecules of the modifying agent being added to this tryptophan side chain. The modification apparently does not cause a detectable conformational change of the protein as judged from the methods employed. However, the enzymatic activities in the dehydrogenase as well as in the esterase reactions are lost after the modification. It could be established that the modification rendered the enzyme unable to bind the oxidized coenzyme. Also the charge-transfer interaction between enzyme and coenzyme could no longer be observed.

Apoproteins↗
PubMed1975

The effect of plasma on the reaction of cyclophosphamide with 4(-p-nitrobenzyl)-pyridine.

Cyclophosphamide is not structurally modified by blood plasma and may be recovered quantitatively from it. The apparent loss of alkylating ability of cyclophosphamide, as measured by its ability to react with 4-(p-nitrobenzyl)-pyridine (NBP), following treatement with plasma is not, as has been reported, due to metabolism of the drug but rather to an inhibition of the colorimetric reaction by a constituent of the plasma. This inhibition is strongly pH dependent, reaching 100% when the pH of the solution of cyclophosphamide in plasma is above 8, and falling to less than 20% when the pH is below 6, but extraction with chloroform at pH 7 separates cyclophosphamide from the inhibitor. Although the nature of the inhibitor has not been elucidated, its presence in plasma is of great importance in the quantitative determination of cyclophosphamide, and may also be of significance in the biological effects of cyclophosphamide and other alkylating agents in vivo.

Alkylating Agents↗
PubMed2006

Cosorption study of organic pollutants and dissolved organic matter in a soil.

In this study we have evaluated the effects of dissolved organic matter (DOM) on sorption of imidacloprid, 3,4-dichloroaniline (3,4-DCA) and 4-bromoaniline (4-BA) on a typical calcareous soil (Luvic Xerosol) from south-eastern Spain. Two different types of DOM were used, that is to say, dissolved natural organic matter extracts from a commercial peat (DNOM) and a high-purity tannic acid (TA) solution. The experiments were carried out in a 0.01 M CaCl2 aqueous medium at 25 degrees C. The results indicated that the presence of both DNOM and TA, over a concentration range of 15-100 mg L(-1), produced an increase in the amount of 3,4-DCA and 4-BA sorbed and a decrease in the amount of imidacloprid retained on the soil studied. A modified distribution coefficient, K(doc), has been proposed as a safer parameter for soil sorption predictions of organic pollutants and it could be of help to model the fate of these in the environment.

Adsorption↗
PubMed2001

Treatment methods for the remediation of nitroaromatic explosives.

The production and use of nitroaromatic explosives for military operations have resulted in their dissemination into the environment, where their presence in waterways and soil poses an ecological and health hazard. This paper reviews technologies that are available or under investigation to remediate areas contaminated with these compounds.

Adsorption↗
PubMed1999

In vivo effects of new inhibitors of catechol-O-methyl transferase.

1. The effects of two new synthetic compounds showing in vitro catechol-O-methyl transferase (COMT) inhibitor properties were studied in vivo and compared with the effects of nitecapone and Ro-41-0960. 2. QO IA (3-(3-hydroxy-4-methoxy-5-nitrobenzylidene)-2,4-pentanedione), QO IIR ([2-(3,4-dihydroxy-2-nitrophenyl)vinyl]phenyl ketone), nitecapone and Ro-41-0960 (30 mg kg(-1), i.p.) were given to reserpinized rats 1 h before the administration of L-DOPA/carbidopa (LD/CD, 50:50 mg kg(-1), i.p.). Locomotor activity was assessed 1 h later. All the COMT inhibitors (COMTI), with the exception of QO IA, markedly potentiated LD/CD reversal of reserpine-induced akinesia. Similar results were obtained when the COMTI were coadministered with LD/CD. The effect of compound QO IIR was dose-dependent (7.5-30 mg kg(-1), i.p.). 3. The COMTI (30 mg kg(-1), i.p.) potentiated LD/CD reversal of both catalepsy and hypothermia of reserpinized mice. 4. QO IIR, nitecapone and Ro-41-0960 (30 mg kg(-1), i.p.) reduced striatal 3-methyl-DOPA (3-OMD) levels and increased dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) levels. Compound QO IA was devoid of any effect on striatal amine levels. In contrast to the other inhibitors, Ro-41-0961 reduced HVA levels as well. The effect of QO IIR on striatal amine levels was dose-dependent (7.5-60 mg kg(-1), i.p.) 5. These results suggest that the new compound QO IIR is an effective peripherally acting COMT inhibitor in vivo.

Animals↗
PubMed1984

Relationship between the chemical structure and the mutagenic and carcinogenic potentials of five naphthofurans.

We have analyzed the relationship between the biological activities and chemical structure of five naphthofurans. The compounds studied included 2-nitro-7-methoxynaphtho[2,1-b]-furan (R 7000) (Compound A), 2-nitro-8-methoxynaphtho[2,1-b]-furan (Compound B), 2-nitronaphtho[2,1-b]furan (Compound C), 2-nitro-7-bromonaphtho[2,1-b]furan (Compound D), and 7-methoxynaphtho[2,1-b]furan (Compound E), the nonnitrated analogue of Compound A. The genotoxic activities of the compounds were studied in V79 cells using the micronucleus, sister chromatid exchange, and hypoxanthine-guanine phosphoribosyltransferase locus mutation tests. This allowed us to classify their mutagenic properties in the following order: A congruent to B much greater than C greater than D greater than E. However, in the in vivo short-term skin tests, the order in activities of the first three compounds is reversed, and the five compounds can be classified in decreasing rank of potency: C greater than B greater than A greater than or equal to E congruent to D. The two compounds tested for in vitro transformation, Compounds A and B, demonstrated a positive effect in both the C3H10T1/2 and the Syrian hamster embryo cell systems. The biological activities of Compounds A, B, C, and D appeared to be strongly linked to the presence of a NO2 group in position 2. These activities were enhanced or decreased by a methoxy group in position 7 or 8. Almost all activities were suppressed if the methoxy group in position 7 was replaced by a bromine (Compound D). The positive results obtained in the cell transformation assays and in the short-term skin tests indicate that Compounds A, B, and C are probably carcinogenic. Therefore, further in vivo studies should be accomplished before using the 2-nitronaphthofuran derivatives in human and animal treatments.

Animals↗
PubMed1998

Inhibition of human platelet aggregation by diazeniumdiolates: extent of inhibition correlates with nitric oxide load delivered.

The profile of nitric oxide (NO) release from the diazeniumdiolate class of NO donors was evaluated using inhibition of platelet aggregation as a model. At 37 degrees C, the NO complexes (Z)-1-¿N-methyl-N-[6-(N-methylammoniohexyl)amino]¿-diazen-1- ium-1,2-diolate (dimethylhexanediamine complex), sodium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (diethylamine complex), (Z)-1-¿N-[3-aminopropyl]-N-[4-(3-aminopropylammonio)butyl]amino diazen-1-ium-1,2-diolate (spermine complex), and (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1- ium-1,2-diolate (diethylenetriamine complex) have half-lives of 1, 2 and 39 min, and 20 h, respectively. All the diazeniumdiolates caused concentration-dependent inhibition of platelet aggregation; IC50 values (values for which the effect was half the maximum) were 26.0+/-24.1, 34.9+/-24.0 and 14.9+/-6.4 nM for dimethylhexanediamine complex, diethylamine complex and spermine complex, respectively, when pre-incubated with platelets for one half-life. Inhibition by all compounds was time-dependent. Pretreatment of platelets with spermine complex for 5 and 39 min resulted in IC50 values of 1.7+/-0.85 microM and 19.7+/-0.12 nM, whereas IC50 values for sodium nitroprusside were 27.3+/-1.25 nM and 25 nM (average, n = 2), at 5 and 39 min, respectively. Pre-incubation of each diazeniumdiolate at a concentration of 100 nM for 5 min at 37 degrees C, which resulted in the theoretical delivery of NO loads from 96.9% down to 0.3%, resulted in decreasingly efficacious inhibition of platelet aggregation. Linear regression analysis of the theoretical NO load delivered against the actual maximum inhibition (%) showed a strong correlation (r2 = 0.975). All four diazeniumdiolates caused concentration- and time-dependent inhibition of agonist-stimulated elevation of intra-platelet Ca2+ levels; IC50 values were, respectively, 8.7+/-1.49 nM and 11.5+/-1.36 nM for dimethylhexanediamine complex and diethylamine complex at their half-lives, and 176+/-16.9 nM and >100 microM, for spermine complex and diethylenetriamine complex at 2 min pre-incubation time. The respective nucleophiles not complexed with NO did not show anti-aggregatory properties or inhibition of agonist-induced elevation of intra-platelet Ca2+ levels. The inhibitory effects of all diazeniumdiolates tested were attenuated by 10 microM haemoglobin. These studies indicate that these compounds induce controlled, predictable release of NO at biological pH and temperature.

Blood Platelets↗