Journal of enzyme inhibition最新文献_第9页

Glucosylated isoflavones as DNA topoisomerase II poisons. 糖基化异黄酮作为DNA拓扑异构酶II毒物。

Journal of enzyme inhibition Pub Date : 2000-01-01 DOI: 10.3109/14756360009040701

C Martín-Cordero, M López-Lazaro, J Piñero, T Ortiz, F Cortés, M J Ayuso

引用次数: 26

Dye affinity labelling of yeast alcohol dehydrogenase. 酵母醇脱氢酶的染料亲和标记。

Journal of enzyme inhibition Pub Date : 2000-01-01 DOI: 10.3109/14756360009040704

N E Labrou

引用次数: 4

Carbonic anhydrase inhibitors. metal complexes of 5-(2-chlorophenyl)-1,3,4-thiadiazole-2-sulfonamide with topical intraocular pressure lowering properties: the influence of metal ions upon the pharmacological activity. 碳酸酐酶抑制剂。5-(2-氯苯基)-1,3,4-噻二唑-2-磺酰胺的金属配合物具有局部降低眼压的特性:金属离子对其药理活性的影响

Journal of enzyme inhibition Pub Date : 2000-01-01 DOI: 10.1080/14756360009030350

F Briganti, S Tilli, G Mincione, F Mincione, L Menabuoni, C T Supuran

{"title":"Carbonic anhydrase inhibitors. metal complexes of 5-(2-chlorophenyl)-1,3,4-thiadiazole-2-sulfonamide with topical intraocular pressure lowering properties: the influence of metal ions upon the pharmacological activity.","authors":"F Briganti, S Tilli, G Mincione, F Mincione, L Menabuoni, C T Supuran","doi":"10.1080/14756360009030350","DOIUrl":"https://doi.org/10.1080/14756360009030350","url":null,"abstract":"Metal complexes of a sulfonamide possessing strong carbonic anhydrase (CA) inhibitory properties, 5-(2-chlorophenyl)-1,3,4-thiadiazole-2-sulfonamide (chlorazolamide) have been obtained from the sodium salt of the sulfonamide and the following metal ions: Mg(II), Zn(II), Mn(II), Cu(II), Co(II), Ni(II), Be(II), Cd(II), Pb(II), Al(III), Fe(III) and La(III). The original sulfonamide and its complexes were assayed for the in vitro inhibition of three CA isozymes, CA I, II, and IV, some of which play a critical role in ocular fluid secretion. All these compounds (the sulfonamide and its metal complexes) behaved as powerful inhibitors against the three investigated isozymes. The parent sulfonamide possessed an extremely weak topical pressure lowering effect when administered as a 1-2% suspension into the rabbit eye, but some of its metal complexes, such as the Mg(II), Zn(II), Mn(II) and Cu(II) derivatives, lower intraocular pressure (IOP) in experimental animals very well. Ex vivo data showed a 99.5-99.9% CA II inhibition in ocular fluids and tissues of rabbits treated with these agents, proving that the observed IOP lowering is due to CA inhibition. The influence of the different metal ions upon the efficiency of the obtained complexes as pressure lowering drugs are discussed, leading to the possibility of designing more selective/potent pharmacological agents from this class.","PeriodicalId":15776,"journal":{"name":"Journal of enzyme inhibition","volume":"15 2","pages":"185-200"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/14756360009030350","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21777234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 16

The kinetic mechanism of 5-enolpyruvylshikimate-3-phosphate synthase from a gram-positive pathogen Streptococcus pneumoniae. 来自革兰氏阳性病原体肺炎链球菌的 5-烯醇丙酮酰莽草酸-3-磷酸合成酶的动力学机制。

Journal of enzyme inhibition Pub Date : 2000-01-01 DOI: 10.3109/14756360009040711

W Du, N G Wallis, D J Payne

{"title":"The kinetic mechanism of 5-enolpyruvylshikimate-3-phosphate synthase from a gram-positive pathogen Streptococcus pneumoniae.","authors":"W Du, N G Wallis, D J Payne","doi":"10.3109/14756360009040711","DOIUrl":"10.3109/14756360009040711","url":null,"abstract":"The Streptococcus pneumoniae 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase is a potential novel antibacterial target. The enzyme catalyzes a reversible transfer of an enolpyruvyl group from phospho(enol)pyruvate (PEP) to shikimate 3-phosphate (S3P) to give EPSP with the release of inorganic phosphate (Pi). Understanding the kinetic mechanism of this enzyme is crucial to the design of novel inhibitors of this enzyme that may have potential as antibacterial agents. Steady-state kinetic studies of product inhibition and inhibition by glyphosate (GLP) have demonstrated diverse inhibition patterns of the enzyme. In the forward reaction, GLP is a competitive inhibitor with respect to PEP, but an uncompetitive inhibitor relative to S3P. Product inhibition shows that EPSP is a competitive inhibitor versus both PEP and S3P, suggesting that the forward reaction follows a random sequential mechanism. In the reverse reaction, GLP is an uncompetitive inhibitor versus EPSP, but a noncompetitive inhibitor versus Pi. This indicates that a non-productive quaternary complex might be formed between the enzyme, EPSP, GLP and Pi. Product inhibition in the reverse reaction has also been investigated. The inhibition patterns of the S. pneumoniae EPSP synthase are not entirely consistent with those of EPSP synthases from other species, indicating that EPSP synthases from different organisms may adopt unique mechanisms to catalyze the same reactions.","PeriodicalId":15776,"journal":{"name":"Journal of enzyme inhibition","volume":"15 6","pages":"571-81"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/14756360009040711","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21962458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

Use of a bisubstrate inhibitor to distinguish between isocitrate dehydrogenase isozymes. 使用二底物抑制剂来区分异柠檬酸脱氢酶同工酶。

Journal of enzyme inhibition Pub Date : 2000-01-01 DOI: 10.3109/14756360009040687

R S Ehrlich

引用次数: 1

Carbonic anhydrase activators: synthesis of high affinity isozymes I, II and IV activators, derivatives of 4-(4-tosylureido-amino acyl)ethyl-1H-imidazole (histamine derivatives). 碳酸酐酶激活剂:合成高亲和力同工酶I, II和IV激活剂，4-(4-甲酰基-氨基酰基)乙基- 1h -咪唑(组胺衍生物)的衍生物。

Journal of enzyme inhibition Pub Date : 2000-01-01 DOI: 10.1080/14756360009030347

A Scozzafava, B Iorga, C T Supuran

{"title":"Carbonic anhydrase activators: synthesis of high affinity isozymes I, II and IV activators, derivatives of 4-(4-tosylureido-amino acyl)ethyl-1H-imidazole (histamine derivatives).","authors":"A Scozzafava, B Iorga, C T Supuran","doi":"10.1080/14756360009030347","DOIUrl":"https://doi.org/10.1080/14756360009030347","url":null,"abstract":"Reaction of histamine (Hst) with tetrabromophthalic anhydride and protection of its imidazole moiety with tritylsulfenyl chloride, followed by hydrazinolysis, afforded N-1-tritylsulfenyl histamine, a key intermediate which was further derivatized at its aminoethyl moiety. Reaction of the key intermediate with 4-tosylureido amino acids/dipeptides (ts-AA) in the presence of carbodiimides, afforded after deprotection of the imidazole moiety, a series of compounds with the general formula ts-AA-Hst (ts=4-MeC(6) H(4) SO(2) NHCO). Some structurally related dipeptide derivatives with the general formula ts-AA1-AA2-Hst, were also prepared, by in a similar way to the amino acyl compounds mentioned above. The new derivatives were examined as activators of three carbonic anhydrase (CA) isozymes, hCA I, hCA II (cytosolic forms) and bCA IV (membrane-bound form). Efficient activation was observed against all three isozymes, but especially against hCA I and bCA IV, with affinities in the 1-10 nanomolar range for the best compounds. hCA II was on the other hand activatable with affinities around 20-50 nM. This new class of CA activators might lead to the development of drugs/diagnostic agents for the CA deficiency syndrome, a genetic disease of bone, brain and kidneys.","PeriodicalId":15776,"journal":{"name":"Journal of enzyme inhibition","volume":"15 2","pages":"139-61"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/14756360009030347","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21777231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 30

Cadmium inhibition of a structural wheat peroxidase. 镉对小麦结构过氧化物酶的抑制作用。

Journal of enzyme inhibition Pub Date : 2000-01-01 DOI: 10.1080/14756360009030349

D A Converso, M E Fernández, M L Tomaro

引用次数: 15

Synthesis and mechanism of action of novel thiocarbamate inhibitors of human leukocyte elastase. 新型人白细胞弹性酶硫代氨基甲酸酯抑制剂的合成及其作用机制。

Journal of enzyme inhibition Pub Date : 2000-01-01

Z S Li-Pan, H V Joshi, G A Digenis

引用次数: 0

Inhibition of acidic sphingomyelinase by xanthone compounds isolated from Garcinia speciosa. 藤黄黄酮化合物对酸性鞘磷脂酶的抑制作用。

Journal of enzyme inhibition Pub Date : 2000-01-01 DOI: 10.1080/14756360009030346

C Okudaira, Y Ikeda, S Kondo, S Furuya, Y Hirabayashi, T Koyano, Y Saito, K Umezawa

引用次数: 37

Protease inhibitors: Part 4. Synthesis of weakly basic thrombin inhibitors incorporating pyridinium-sulfanilylaminoguanidine moieties. 蛋白酶抑制剂:第4部分。含吡啶-磺胺基氨基胍的弱碱性凝血酶抑制剂的合成。

Journal of enzyme inhibition Pub Date : 2000-01-01 DOI: 10.1080/14756360009040692

C T Supuran, F Briganti, A Scozzafava, M A Ilies

{"title":"Protease inhibitors: Part 4. Synthesis of weakly basic thrombin inhibitors incorporating pyridinium-sulfanilylaminoguanidine moieties.","authors":"C T Supuran, F Briganti, A Scozzafava, M A Ilies","doi":"10.1080/14756360009040692","DOIUrl":"https://doi.org/10.1080/14756360009040692","url":null,"abstract":"Three series of derivatives have been prepared by reaction of sulfanilylaminoguanidine with pyrylium salts, with the pyridinium derivatives of glycine and with the pyridinium derivatives of beta-alanine, respectively. The new compounds were assayed as inhibitors of two serine proteases, thrombin and trypsin. The study showed that in contrast to the leads, possessing KI's around 100-300 nM against thrombin, and 450-1420 nM against trypsin, respectively, the new derivatives showed inhibition constants in the range of 15-50 nM against thrombin, whereas their affinity for trypsin remained relatively low. Derivatives of beta-alanine were more active than the corresponding glycine derivatives, which in turn were more inhibitory than the pyridinium derivatives of sulfanilylaminoguanidine possessing the same substitution pattern at the pyridinium ring. Thus, the present study proposes two novel approaches for the preparation of high affinity, specific thrombin inhibitors: a novel S1 anchoring moiety in the already large family of arginine/amidine-based inhibitors, i.e., the SO2NHNHC(=NH)NH2 group, and novel non-peptidomimetic scaffolds obtained by incorporating alkyl-/aryl-substituted-pyridinium moieties in the hydrophobic binding site(s). The first one is important for obtaining bioavailable thrombin inhibitors, devoid of the high basicity of the commonly used arginine/amidine-based inhibitors, whereas the second one may lead to improved water solubility of such compounds.","PeriodicalId":15776,"journal":{"name":"Journal of enzyme inhibition","volume":"15 4","pages":"335-56"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/14756360009040692","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21829021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0