Journal of enzyme inhibition最新文献_第3页

Effects of Substrate Structural Analogues on the Enzymatic Activities of Aspartate Aminotransferase Isoenzymes 底物结构类似物对天冬氨酸转氨酶同工酶活性的影响

Journal of enzyme inhibition Pub Date : 2001-01-01 DOI: 10.1080/14756360109162373

L. L. Martins, M. Mourato, A. de Varennes

引用次数: 2

Enantioselectivity of Some 1-[(Benzofuran-2-yl) phenylmethyl] imidazoles as Aromatase (P450AROM) Inhibitors 一些1-[(苯并呋喃-2-基)苯基甲基]咪唑作为芳香化酶抑制剂的对映选择性

Journal of enzyme inhibition Pub Date : 2001-01-01 DOI: 10.1080/14756360109162389

G. Khodarahmi, C. Laughton, H. Smith, P. Nicholls

{"title":"Enantioselectivity of Some 1-[(Benzofuran-2-yl) phenylmethyl] imidazoles as Aromatase (P450AROM) Inhibitors","authors":"G. Khodarahmi, C. Laughton, H. Smith, P. Nicholls","doi":"10.1080/14756360109162389","DOIUrl":"https://doi.org/10.1080/14756360109162389","url":null,"abstract":"The enantioselectivity ratio ((+)-:(-)-forms) of three substituted 1-[(benzofuran-2-yI) phenylmethyl] imidazoles as inhibitors of aromatase (P450AROM) was 2.16, 12.3 and 1.0 for the 4-methyl-, 4-fluoro- and 4-chloro-substituted compounds, respectively. The (±)-compounds were all >1000 times more potent than (±)-aminoglutethimide (IC50 = 12 × 103 nM). High potency (5.3–65.0 nM) for all the enantiomers studied is unusual since activity usually resides in one form for chiral inhibitors of P450AROM- The 4-methyl derivative was fitted into the model [Furet, P., Batzl, C., Bhatnager, A.S., Francotte, E., Rihs, G. and Lang, M. (1993) J. Med. Chem. 36, pp. 1393–1400] for binding of S-(-)-fadrazole to the active site and the (R)- and (S)- forms both gave a good fitting pattern with (S)-(-)-fadrazole so accounting for their close activity. Docking of both forms into the active site model for P450AROM [Laughton, C.A., Zvelebil, M.J.J.M. and Neidel, S. (1993) J. Steroid Biochem. Mol. Biol. 44, pp. 399–407], using the orientation of (S)-(±)-fadrazole, gave similar strong binding along the position of the C and D rings of the steroid substrate and in the hydrophobic cavity below the A/B rings. The site was probed for group size accommodation using the less potent 4-phenyl analogue (IC50(±) = 242nM): the (S)-form showed restricted access to the region under the A ring due to the extended bulk of the biphenyl group.","PeriodicalId":15776,"journal":{"name":"Journal of enzyme inhibition","volume":"35 3","pages":"401 - 416"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72593030","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: 8

Non-linear Slow-binding Inhibition of Aerococcus viridans Lactate Oxidase by Cibacron Blue 3GA Cibacron Blue 3GA对绿色气球菌乳酸氧化酶的非线性慢结合抑制作用

Journal of enzyme inhibition Pub Date : 2001-01-01 DOI: 10.1080/14756360109162378

S. Streitenberger, J. López-Mas, Á. Sánchez-Ferrer, F. García-Carmona

引用次数: 2

Quantitative Structure-Activity Relationship Study on Tetrahydro-β-carboline Antagonists of the Serotonin 2B (5HT 2B) Contractile Receptor in the Rat Stomach Fundus 大鼠胃底5 -羟色胺2B (5HT 2B)收缩受体四氢β-卡泊碱拮抗剂的定量构效关系研究

Journal of enzyme inhibition Pub Date : 2001-01-01 DOI: 10.1080/14756360127570

P. Singh, Rajesh Kumar

引用次数: 6

Aldose Reductase Inhibitors 醛糖还原酶抑制剂

Journal of enzyme inhibition Pub Date : 2001-01-01 DOI: 10.1080/14756360127568

M. Oka, N. Kato

引用次数: 84

Xanthine Oxidase Catalyzes the Synthesis of Retinoic Acid 黄嘌呤氧化酶催化维甲酸的合成

Journal of enzyme inhibition Pub Date : 2001-01-01 DOI: 10.1080/14756360109162376

G. Taibi, A. Paganini, M. Gueli, F. Ampola, C. Nicotra

{"title":"Xanthine Oxidase Catalyzes the Synthesis of Retinoic Acid","authors":"G. Taibi, A. Paganini, M. Gueli, F. Ampola, C. Nicotra","doi":"10.1080/14756360109162376","DOIUrl":"https://doi.org/10.1080/14756360109162376","url":null,"abstract":"Milk xanthine oxidase (xanthine: oxygen oxidore-ductase; XO; EC 1.1.3.22) was found to catalyze the conversion of retinaldehyde to retinoic acid. The ability of XO to synthesize all trans-retinoic acid efficiently was assessed by its turnover number of 31.56 min−1, determined at pH 7.0 with 1nM XO and all trans-retinaldehyde varying between 0.05 to 2μM. The determination of both retinoid and purine content in milk was also considered in order to correlate their concentrations with kinetic parameters of retinaldehyde oxidase activity. The velocity of the reaction was dependent on the isomeric form of the substrate, the all trans- and 9-cis-forms being the preferred substrates rather than 13-cis-retinaldehyde. The enzyme was able to oxidize retinaldehyde in the presence of oxygen with NAD or without NAD addition. In this latter condition the catalytic efficiency of the enzyme was higher. The synthesis of retinoic acid was inhibited 87% and 54% by 4μM and 2μM allopurinol respectively and inhibited 48% by 10 μM xanthine in enzyme assays performed at 2μM all trans-retinaldehyde. The Ki value determined for xanthine as an inhibitor of retinaldehyde oxidase activity was 4 μM.","PeriodicalId":15776,"journal":{"name":"Journal of enzyme inhibition","volume":"104 1","pages":"275 - 285"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79530663","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: 23

Carbonic Anhydrase Inhibitors, Interaction of Boron Derivatives with Isozymes I and II: A New Binding Site for Hydrophobic Inhibitors at the Entrance of the Active Site as shown by Docking Studies 碳酸酐酶抑制剂，硼衍生物与同工酶I和II的相互作用:对接研究显示疏水抑制剂活性位点入口的新结合位点

Journal of enzyme inhibition Pub Date : 2001-01-01 DOI: 10.1080/14756360109162362

C. Chazalette, M. Rivière-Baudet,, A. Scozzafava, F. Abbate, Zahra Ben Maarouf, C. Supuran

{"title":"Carbonic Anhydrase Inhibitors, Interaction of Boron Derivatives with Isozymes I and II: A New Binding Site for Hydrophobic Inhibitors at the Entrance of the Active Site as shown by Docking Studies","authors":"C. Chazalette, M. Rivière-Baudet,, A. Scozzafava, F. Abbate, Zahra Ben Maarouf, C. Supuran","doi":"10.1080/14756360109162362","DOIUrl":"https://doi.org/10.1080/14756360109162362","url":null,"abstract":"The interaction of human carbonic anhydrase (hCA) isozymes I and II with boron derivatives was investigated by kinetic and spectroscopic studies. These derivatives, tested as new inhibitors of carbonic anhydrase, are sulfonamide and non-sulfonamide boron derivatives and some of them proved to be moderately efficient inhibitors of hCA I and hCA II, their activities being comparable to those of the un-substituted sulfonamides, the classical inhibitors of these zinc enzymes. Ph2BOH, one of the compounds with the highest affinity for hCA II in the present study, has been docked within the active site. After minimisation it was found situated at 7.9 Å from zinc, within the hydrophobic half of the active site, in Van der Waals contacts with the amino acid residues: Val 121, Phe 130, Val 135, Leu 141, Val 143, Val 207 and Pro 201. This is the first time that a CA inhibitor has been found to bind at the edge of the active site cavity, similarly to the CA activator histamine, which binds on the hydrophilic half. This finding may be of importance also for the design of novel types of inhibitors with increased affinity for the different CA isozymes.","PeriodicalId":15776,"journal":{"name":"Journal of enzyme inhibition","volume":"6 1","pages":"125 - 133"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79685814","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: 14

Potential of Pyrazolooxadiazinone Derivatives as Serine Protease Inhibitors 吡唑鲁沙二嗪酮衍生物作为丝氨酸蛋白酶抑制剂的潜力

Journal of enzyme inhibition Pub Date : 2001-01-01 DOI: 10.1080/14756360109162352

C. B. Vicentini, M. Guarneri, V. Andrisano, S. Guccione, Thierry Langer, R. Marschhofer, R. Chabin, A. Edison, X. Huang, W. Knight, P. Giori

{"title":"Potential of Pyrazolooxadiazinone Derivatives as Serine Protease Inhibitors","authors":"C. B. Vicentini, M. Guarneri, V. Andrisano, S. Guccione, Thierry Langer, R. Marschhofer, R. Chabin, A. Edison, X. Huang, W. Knight, P. Giori","doi":"10.1080/14756360109162352","DOIUrl":"https://doi.org/10.1080/14756360109162352","url":null,"abstract":"As a part of an investigation on molecular hybrids as new serine protease inhibitors, the pyrazolo [4,3-c][1,2,5]oxadiazin-3(5H)-one ring system was selected as a model of potential mechanism-based inhibitors. Due to the inherent reactivity of this system an optimal balance between susceptibility to nucleophilic attack and stability in solvents was sought prior to development as therapeutic agents. Substitutions on N5 and C7 of the supporting pyrazole ring with either aliphatic or aromatic groups (compounds 2 a-m) and the replacement of the carbonyl oxygen on the reactive oxadiazinone ring with sulfur (compounds 3a,i) were explored. Two members (2i and 2k) of this class of inhibitors displayed time-dependent inhibition of HLE suggesting mechanism-based inhibition. The observation that HLE generated a product(s) from compound 2i which displayed an identical UV-Visible spectrum to that observed during non-enzymatic hydrolysis further supports this proposal. FlexX-based docking of these compounds into a model of the human leukocyte elastase (HLE) active site produced a molecular model of the inhibitor-enzyme interaction.","PeriodicalId":15776,"journal":{"name":"Journal of enzyme inhibition","volume":"26 1","pages":"15 - 34"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84819595","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: 5

Inhibition of Succinate-cytochrome C Reductase by a Ferromacrocyclic Complex 大环铁络合物对琥珀酸-细胞色素C还原酶的抑制作用

Journal of enzyme inhibition Pub Date : 2001-01-01 DOI: 10.1080/14756360109162387

M. Balbaa, M. Khalifa, M. El-Sabaway, Kamal Kandeelaf

引用次数: 5

Purification and Characterization of Catalase from Chard (Beta vulgaris var. cicla) 甜菜过氧化氢酶的纯化及特性研究

Journal of enzyme inhibition Pub Date : 2001-01-01 DOI: 10.1080/14756360109162366

Ayŝle Dinçler, T. Aydemir

{"title":"Purification and Characterization of Catalase from Chard (Beta vulgaris var. cicla)","authors":"Ayŝle Dinçler, T. Aydemir","doi":"10.1080/14756360109162366","DOIUrl":"https://doi.org/10.1080/14756360109162366","url":null,"abstract":"Catalase is a major primary antioxidant defence component that primarily catalyses the decomposition of H2O2 to H2O. Here we report the purification and characterization of catalase from chard (Beta vulgaris var. cicla). Following a procedure that involved chloroform treatment, ammonium sulfate precipitation and three chromatographic steps (CM-cellulose, Sephadex G-25, and Sephadex G-200), catalase was purified about 250-fold to a final specific activity of 56947 U/mg of protein. The molecular weight of the purified catalase and its subunit were determined to be 235000 and 58500 daltons, indicating that the chard catalase is a tetramer. The absorption spectra showed a soret peak at 406 nm, and there was slightly reduction by dithionite. The ratio of absorption at 406 and 275 nanometers was 1.5, the value being similar to that obtained for catalase from other plant sources. In the catalytic reaction, the apparent Km value for chard catalase was 50 mM. The purified protein has a broad pH optimum for catalase activity between 6.0 and 8.0. The enzyme had an optimum reaction temperature at 30 °C. Heme catalase inhibitors, such as azide and cyanide, inhibited the enzyme activity markedly and the enzyme was also inactivated by β-mercaptoethanol, dithiothreitol and iodoacetamide.","PeriodicalId":15776,"journal":{"name":"Journal of enzyme inhibition","volume":"4 1","pages":"165 - 175"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79986460","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: 18