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Biomedical subjects

G Wurm

Publications and source records attributed to G Wurm.

At least 55 records · Page 3Linked to original sources
PubMed1985

Interactions of a variety of lipoxygenase inhibitors with a supplementary binding site on soybean lipoxygenase.

Studies on the combined effects of a variety of lipoxygenase inhibitors and cyclo-oxygenase inhibitors revealed strong evidence for the existence of supplementary binding sites on lipoxygenases which modify the reactions of inhibitors with the catalytic site of the enzyme. Independent of their low or non-existent inhibitory reaction at the catalytic site, compounds which interact more effectively with this putative supplementary site are capable of blunting the inhibitory efficacy of potent lipoxygenase inhibitors. Although the degree of interaction with the catalytic site determines the potency of inhibitors, an additional reaction at the supplementary site is also obligatory for inhibitory efficacy. We found that potent lipoxygenase inhibitors possess high affinities for both sites, whereas weak inhibitors and suitable cyclo-oxygenase inhibitors interact predominantly with the supplementary site on the lipoxygenase and possess low or negligible affinities for its catalytic site.

Acetone↗
PubMed1984

Studies on the possible involvement of singlet oxygen and superoxide anion radicals in the cyclo-oxygenase reaction.

The influence of several naphthalene and furan derivatives which are potent singlet oxygen (1O2) acceptors on two prostaglandin synthetase preparations derived from bovine seminal vesicles or rat kidney medulla was studied. Also the effects on the formation of superoxide anion radicals (O2-.) were measured to give further evidence for or against the possible involvement of 1O2 or O2-. in the cyclo-oxygenase reaction. The data we have attained make an essential role of these activated oxygen species as initiators of the cyclo-oxygenase reaction unlikely and thereby support the hypothesis that cyclo-oxygenation during prostaglandin biosynthesis is a lipoxygenase type of reaction.

Animals↗
PubMed1984

Interactions of inhibitors of the lipoxygenase and cyclooxygenase pathways with a supplementary binding site on soybean lipoxygenase.

The oxygenation of [1-14C]-arachidonic acid by a soluble soybean lipoxygenase (E.C.1.13.11.12) preparation was determined in the presence of various cyclo-oxygenase and lipoxygenase inhibitors. The results showed that several non-inhibitory compounds drastically blunted the inhibitory potency of potent lipoxygenase inhibitors. Studies on the combined effects of a variety of structurally unrelated inhibitors of lipoxygenase, cyclo-oxygenase or both oxygenation pathways provided strong evidence for the existence of a supplementary binding site on soybean lipoxygenase which reduces the effective interactions of inhibitors with the catalytic site. Thus several cyclo-oxygenase inhibitors (which do not inhibit at the lipoxygenase catalytic site), as well as low concentrations of lipoxygenase inhibitors, interact with this putative supplementary site and blunt the inhibitory efficacy of potent lipoxygenase inhibitors. Although the degree of interaction with the catalytic site determines the absolute potency of inhibitors, the additional interaction at the putative supplementary binding site is also obligatory for inhibitory potency. In this new multiple-site model the potent lipoxygenase inhibitors (e.g. acetone phenylhydrazone, phenidone) possess high affinities for both sites, whereas weak inhibitors and certain cyclo-oxygenase inhibitors (e.g. benoxaprofen, phenylbutazone, indomethacin) interact predominantly with the supplementary site on the lipoxygenase but lack affinity for the catalytic site.

Binding Sites↗
PubMed1984

[Lipophilic naphthols and 1,4-naphthoquinones as inhibitors of prostaglandin synthesis. 6. Study of 1,4-naphthoquinones].

A number of plumgagin homologues (2-alkyl-1,4-naphthoquinones) and their 3-methyl derivatives are synthesized to enhance the inhibition of the prostaglandin synthetase (PGS)-activity by the natural compound plumbagin and to minimize its toxicity. The inhibition of the enzyme activity by the new naphthoquinones is only weak but their naphthol precursors are strong PGS-inhibitors. The mechanism of this enzyme interaction by the lipophilic naphthol derivatives is discussed in context with their singlet oxygen (1O2) reactive properties.

Animals↗
PubMed1984

In vitro deacetylation studies of acetamidophenolic compounds in rat brain, liver and kidney.

The in vitro deacetylation of ortho-, meta- and para-substituted acetophenetidines and acetamidophenols including acetanilide by arylacylamidases in rat brain, liver and kidney was investigated. In general, deacetylation rates were highest in liver and kidney preparations, whereas brain exhibited lower enzyme activities. Acetophenetidines were more suitable N-deacetylation substrates in comparison to acetamidophenols, whereby o-substituted compounds were split more easily than their corresponding m- or p-analogues. Among the arylacylamides tested, o-acetophenetidine was the predominant substrate in all tissues. It was deacetylated by far more rapidly than phenacetin. The enzymic deacetylation of acetophenetidines in kidney and brain was inhibited by p-nitrophenylacetate revealing that N-acetylamides as well as O-acetyl esters undergo similar degradation by carboxylesterase-amidases. The organophosphorous diester bis(p-nitrophenyl)-phosphate which is known to be a rather selective inhibitor of acetanilide-cleaving hydrolases in rat liver suppressed the deacetylation of acetanilide in all tissues investigated. In contrast to acetanilide, the deacetylation of acetophenetidines was inhibited by bis(p-nitrophenyl)-phosphate in liver and kidney, but bis(p-nitrophenyl)-phosphate was by far less active against acetophenetidine hydrolases in brain.

Acetamides↗
PubMed1983

Inhibition of prostaglandin synthetases derived from neuronal and glial cells and rat renal medulla by ortho-, meta- and para-substituted aminophenolic compounds.

Acetophenetidines, acetamidophenols, phenetidines and aminophenols substituted in o-, m- or p-position inhibit prostaglandin-synthetases originating from C 1300 mouse neuroblastoma cells (clone N2A), rat astrocytoma cells (clone C 6) and rat renal medulla. Desacetylated compounds were more potent inhibitors than their corresponding acetyl derivatives and many o- and m-analogues were more active than p-substituted structures like paracetamol (p-acetamidophenol) or phenacetin (p-acetophenetidine). When twelve o-, m- or p-aminophenolic test compounds were compared to acetylsalicyclic acid and indomethacin, o-, and p-phenetidine and o-aminophenol were as effective as acetylsalicyclic acid. All aminophenol derivatives which inhibited prostaglandin synthesis suppressed cultured nervous cell and kidney cyclo-oxygenases to similar extents. Our results suggest that aminophenolic drugs are not more effective against prostaglandin-synthetases in the CNS than against those in the periphery.

Acetaminophen↗
PubMed1983

Decreasing inhibitory potency of prostaglandin synthetase inhibitors during their cooxidative metabolism. Studies on aminophenols, pyrazolon derivatives and 1,3-diphenylisobenzofuran.

A variety of prostaglandin synthetase inhibitors are cooxygenated during arachidonic acid peroxidation catalyzed by rat renal medulla prostaglandin synthetase or soybean lipoxygenase. Phenylbutazone, aminopyrine, 1,3-diphenylisobenzofuran, paracetamol, p-aminophenol, p-phenetidine and other o- and m-substituted aminophenol derivatives were cooxygenated, whereby prostaglandin synthetase inhibition was significantly weakened due to the formation of less inhibitory metabolites. In contrast, the inhibitory potency of diclofenac, indomethacin and phenacetin and its analogues remained unchanged during prostaglandin synthesis inhibition, because these compounds were no suitable cooxygenation substrates. Evidence is given that quinone imines may not be involved in the cooxidative metabolism of paracetamol and other aminophenols. As to the mechanisms of cooxygenation of suitable substrates dependent on their chemical structures either the arachidonic acid oxygenase or the subsequent hydroperoxidase reaction may trigger the oxygenation. 1,3-Diphenylisobenzofuran is metabolized during the formation of arachidonic acid hydroperoxides in contrast to paracetamol, which requires an additional peroxidase reaction to yield reactive metabolites.

Acetaminophen↗
PubMed1982

Soybean lipoxygenase-1 inhibition by ketone hydrazones.

Acetone phenylhydrazone has recently been discovered as a predominant inhibitor of arachidonic acid lipoxygenase in platelets [1]. We found that besides this compound a variety of hydrazones derived from other ketones and hydrazines exhibited similar or more interesting inhibition patterns both against soybean lipoxygenase and rat renal prostaglandin synthetase. Depending on their molecular structure, relatively selective inhibitors of the two arachidonate peroxidation pathways are introduced which may be useful tools for further investigation of the fatty acid oxygenation cascade.

Animals↗
PubMed1981

[Influence of Hydroxy-1,4-naphthoquinone Derivatives on Prostaglandin synthesis (author's transl)].

Inhibition of cyclo-oxygenase reaction during prostaglandin formation in the renal medulla of the rat by 1,4-naphthoquinone derivatives is compared with the known enzyme inhibition properties of natural and synthetic flavonols. Structure-activity relationship study shows strong correlation between chemical properties (vicinal hydroxy-oxo structure of planar molecules) and physicochemical parameters (polarity and acidity). The most potent compounds are 2-ethyl-5-hydroxy-1,4-naphthoquinone (9) and 2-methyl-3-hydroxy-1,4-naphthoquinone (6).

Animals↗
PubMed1980

Flavonoids and related compounds as inhibition of arachidonic acid peroxidation.

Until now only few data have been reported on biochemically explicable pharmacological effects of flavonoid structures. When tested against arachidonic acid metabolism many flavonoids were found to be effective against the lipoxygenase and cyclo-oxygenase pathways. Some flavonoids were predominant inhibitors of either cyclo-oxygenase or lipoxygenase, others were equally effective against both enzymes. Therefore, these compounds proved to be useful tools to elucidate fatty acid peroxidation problems.

Animals↗
PubMed1979

A structure-activity study on the influence of phenolic compounds and bioflavonoids on rat renal prostaglandin synthetase.

The stimulating or inhibiting influences of 33 phenolic compounds on the prostaglandin synthetase of rat renal medulla were tested. Dihydroxyphenylcarbonic acids clearly proved to be activators of the prostaglandin synthetase. Dimethoxyphenylcarbonic acids were ineffective. Aminoethylphenols as well as p-substituted monohydroxybenzenes with a carbonic acid side chain were clear stimulators in contrast to their alkyl derivatives which are pronounced inhibitors. Among the tested bioflavonoids (+)-cyanidanol-3 and morin were inhibitors of the prostaglandin synthesis. Flavonoids with polar substitution in 3,5,7-position such as rutin on the other hand showed activating properties.

Animals↗
PubMed1979

[Structure-activity studies on carboxyflavone derivatives with antianaphylactic activity (author's transl)].

The passive cutaneous anaphylaxis (PCA) activities of a number of new A- and B-ring carboxyflavone and carboxyflavonol derivatives with planar and without planar orientation of the B-ring--synthesized in relation to baicalein and 2-carboxyxanthone derivatives as antianaphylactic prototypes--are recorded. From the investigated compounds A-ring carboxylic acids are more active than B-ring carboxy derivatives and flavonols are less active than flavones. Problems resulting from the correlation of the PCA activity of a number of chromone derivatives with the substitution of the 3-position are discussed.

Animals↗