Journal of enzyme inhibition最新文献_第10页

The antifungal activity of sulfonylated/carboxylated derivatives of dibenzo-1,4-dioxine-2-acetyloxime may be due to inhibition of lanosterol-14alpha-demethylase. 二苯并-1,4-二恶英-2-乙酰氧肟磺化/羧化衍生物的抗真菌活性可能是由于抑制羊毛甾醇-14 α -去甲基化酶。

Journal of enzyme inhibition Pub Date : 2000-01-01 DOI: 10.3109/14756360009040710

A Mastrolorenzo, A Scozzafava, C T Supuran

{"title":"The antifungal activity of sulfonylated/carboxylated derivatives of dibenzo-1,4-dioxine-2-acetyloxime may be due to inhibition of lanosterol-14alpha-demethylase.","authors":"A Mastrolorenzo, A Scozzafava, C T Supuran","doi":"10.3109/14756360009040710","DOIUrl":"https://doi.org/10.3109/14756360009040710","url":null,"abstract":"Aryl/alkyl-sulfonyl-, aryl/alkylcarboxyl- and aryl(sulfonyl)carbamyl/thiocarbamyl-derivatives of dibenzo-1,4-dioxine-2-acetyloxime were prepared by reaction of the title compound with sulfonyl halides, sulfonic acid anhydrides, acyl chlorides/carboxylic acids, arylsulfonyl isocyanates, aryl/acyl isocyanates or isothiocyanates. Several of the newly synthesized compounds showed effective in vitro antifungal activity against Aspergillus and Candida spp., some of them showing activities comparable to ketoconazole (with minimum inhibitory concentrations in the range of 1.2-4 microg/mL) against the two Aspergillus strains, but possessing a lower activity as compared to ketoconazole against C. albicans. Of the three investigated strains, best activity was detected against A. flavus. The mechanism of action of these compounds probably involves inhibition of ergosterol biosynthesis by interaction with lanosterol-14-alpha-demethylase (CYP51A1), since reduced amounts of ergosterol were found by means of HPLC, in cultures of the sensitive strain A. flavus treated with some of these inhibitors. Thus, the compounds reported here might possess a similar mechanism of action at molecular level with that of the widely used azole antifungals.","PeriodicalId":15776,"journal":{"name":"Journal of enzyme inhibition","volume":"15 6","pages":"557-69"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/14756360009040710","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21962457","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: 3

Antifungal activity of Ag(I) and Zn(II) complexes of aminobenzolamide (5-sulfanilylamido-1,3,4-thiadiazole-2-sulfonamide) derivatives. 氨基苯并胺(5-磺酰基酰胺-1,3,4-噻二唑-2-磺酰胺)衍生物Ag(I)和Zn(II)配合物的抗真菌活性

Journal of enzyme inhibition Pub Date : 2000-01-01 DOI: 10.3109/14756360009040707

A Mastrolorenzo, A Scozzafava, C T Supuran

{"title":"Antifungal activity of Ag(I) and Zn(II) complexes of aminobenzolamide (5-sulfanilylamido-1,3,4-thiadiazole-2-sulfonamide) derivatives.","authors":"A Mastrolorenzo, A Scozzafava, C T Supuran","doi":"10.3109/14756360009040707","DOIUrl":"https://doi.org/10.3109/14756360009040707","url":null,"abstract":"Aminobenzolamide (5-sulfanilylamido-1,3,4-thiadiazole-2-sulfonamide) is a potent inhibitor of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), being at the same time structurally similar to the antimicrobial sulfonamides. Here we report that the reaction of aminobenzolamide with arylsulfonyl isocyanates affords a series of new arylsulfonylureido derivatives which were subsequently used as ligands (in the form of conjugate bases, as sulfonamide anions) for the preparation of metal complexes containing Ag(I) and Zn(II). All the new compounds proved to be very potent inhibitors of CA (isozymes I, II and IV). The newly synthesized complexes, unlike the free ligands, also act as effective antifungal agents against several Aspergillus and Candida spp., some of them showing activities comparable to ketoconazole, with minimum inhibitory concentrations in the range of 1.8-5 microg/mL. The mechanism of antifungal action of these complexes seem to be unconnected with inhibition of lanosterol-14-alpha-demethylase, since the levels of sterols assessed in the fungi cultures were equal in the absence or in the presence of the tested compounds. Probably the new complexes act as inhibitors of phosphomannose isomerase, a key enzyme in the biosynthesis of yeast cell walls.","PeriodicalId":15776,"journal":{"name":"Journal of enzyme inhibition","volume":"15 6","pages":"517-31"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/14756360009040707","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21963214","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

Inhibition of acid phosphatase isoforms purified from mature soybean (Glycine max) seeds. 抑制从成熟大豆（Glycine max）种子中提纯的酸性磷酸酶同工酶。

Journal of enzyme inhibition Pub Date : 2000-01-01 DOI: 10.1080/14756360009040696

C V Ferreira, E M Taga, H Aoyama

引用次数: 10

Non-enzymatic glycosylation (or glycation) and inhibition of the pig heart cytosolic aspartate aminotransferase by glyceraldehyde 3-phosphate. 3-磷酸甘油醛对猪心脏细胞质天冬氨酸转氨酶的非酶糖基化和抑制作用。

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

C Fitzgerald, T A Swearengin, G Yeargans, D McWhorter, B Cucchetti, N W Seidler

引用次数: 0

Protease inhibitors. Part 2. Weakly basic thrombin inhibitors incorporating sulfonyl-aminoguanidine moieties as S1 anchoring groups: synthesis and structure-activity correlations. 蛋白酶抑制剂。第2部分。结合磺酰基氨基胍作为S1锚定基团的弱碱性凝血酶抑制剂:合成和构效相关性。

Journal of enzyme inhibition Pub Date : 2000-01-01 DOI: 10.3109/14756360009040686

B W Clare, A Scozzafava, F Briganti, B Iorga, C T Supuran

{"title":"Protease inhibitors. Part 2. Weakly basic thrombin inhibitors incorporating sulfonyl-aminoguanidine moieties as S1 anchoring groups: synthesis and structure-activity correlations.","authors":"B W Clare, A Scozzafava, F Briganti, B Iorga, C T Supuran","doi":"10.3109/14756360009040686","DOIUrl":"https://doi.org/10.3109/14756360009040686","url":null,"abstract":"Two series of derivatives have been prepared and assayed as inhibitors of two physiologically relevant serine proteases, human thrombin and human trypsin. The first series includes alkyl-/ aralkyl-/aryl- and hetarylsulfonyl-aminoguanidines. It was thus observed that sulfanilyl-aminoguanidine possesses moderate but intrinsically selective thrombin inhibitory properties, with KI values around 90 and 1400 nM against thrombin and trypsin respectively. Further elaboration of this molecule afforded compounds that inhibited thrombin with KI values in the range 10-50 nM, whereas affinity for trypsin remained relatively low. Such compounds were obtained either by attaching benzyloxycarbonyl- or 4-toluenesulfonylureido-protected amino acids (such as D-Phe, L-Pro) or dipeptides (such as Phe-Pro, Gly His, beta-Ala-His or Pro-Gly) to the N-4 atom of the lead molecule, sulfanilyl-aminoguanidine, or by attaching substituted-pyridinium propylcarboxamido moieties to this lead. Thus, this study brings novel insights regarding a novel non-basic S1 anchoring moiety (i.e., SO2NHNHC(=NH)NH2), and new types of peptidomimetic scaffolds obtained by incorporating tosylureido-amino acids/pyridinium-substituted-GABA moieties in the hydrophobic binding site(s). Structure-activity correlations of the new serine protease inhibitors are also discussed based on a QSAR model described previously for a large series of structurally-related derivatives (Supuran et al. (1999) J. Med. Chem., in press).","PeriodicalId":15776,"journal":{"name":"Journal of enzyme inhibition","volume":"15 3","pages":"235-64"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/14756360009040686","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21657735","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: 7

Selective Inhibition of Monoamine Oxidase B by Aminoethyl Substituted Benzyl Ethers. 氨基乙基取代苯醚选择性抑制单胺氧化酶B。

Journal of enzyme inhibition Pub Date : 1999-11-01 DOI: 10.1080/14756369909030338

Woodroofe, Mostashari, Lu, Ramsay, Silverman

{"title":"Selective Inhibition of Monoamine Oxidase B by Aminoethyl Substituted Benzyl Ethers.","authors":"Woodroofe, Mostashari, Lu, Ramsay, Silverman","doi":"10.1080/14756369909030338","DOIUrl":"https://doi.org/10.1080/14756369909030338","url":null,"abstract":"Aminoethyl 3-chlorobenzyl ether was shown previously (Ding, C.Z. and Silverman, R.B. (1993). Bioorg. Med. Chem. Lett., 3, 2077-2078) to be a potent and selective time-dependent, but reversible inhibitor of monoamine oxidase B (MAO B). Based on this result, a series of novel aminoethyl substituted benzyl ethers was synthesized and the compounds were examined as potential inhibitors of both isozymic forms of MAO. Each compound in the series inhibits both MAO A and MAO B competitively, and IC(50) values for each compound were determined. In general, the B isozyme is much more sensitive to these inhibitors than the A isozyme (except for the o- and p-substituted nitro analogues), in some cases by more than two orders of magnitude. The selectivity in favor of MAO B inhibition is relatively high for all of the meta-substituted analogues and quite low for all of the ortho-substituted analogues. Having the substituent at the ortho-position is most favorable for MAO A inhibition. With MAO B the meta-analogues were, in general, more potent than the corresponding ortho- and para-analogues with respect to their reversible binding constants. The meta-iodo analogue is the most potent analogue.","PeriodicalId":15776,"journal":{"name":"Journal of enzyme inhibition","volume":"57 1","pages":"11-21"},"PeriodicalIF":0.0,"publicationDate":"1999-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86698088","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: 2

Carbonic Anhydrase Inhibitors. Synthesis of Topically Effective Intraocular Pressure Lowering Agents Derived from 5-(omega-Amino- alkylcarboxamido)-1,3,4-Thia- diazole-2-Sulfonamide. 碳酸酐酶抑制剂。由5-(ω -氨基-烷基羧胺)-1,3,4-噻二唑-2-磺酰胺衍生的局部有效眼压降压剂的合成。

Journal of enzyme inhibition Pub Date : 1999-11-01 DOI: 10.1080/14756369909030339

Barboiu, Supuran, Menabuoni, Scozzafava, Mincione, Briganti

{"title":"Carbonic Anhydrase Inhibitors. Synthesis of Topically Effective Intraocular Pressure Lowering Agents Derived from 5-(omega-Amino- alkylcarboxamido)-1,3,4-Thia- diazole-2-Sulfonamide.","authors":"Barboiu, Supuran, Menabuoni, Scozzafava, Mincione, Briganti","doi":"10.1080/14756369909030339","DOIUrl":"https://doi.org/10.1080/14756369909030339","url":null,"abstract":"Reaction of the acyl chlorides of phthalimido-glycine or phthalimido-beta-alanine with 5-amino-1,3,4-thiadiazole-2-sulfonamide afforded after hydrazinolysis and deprotection of the phthalimido group the corresponding 5-(omega-aminoalkylcarboxamido)-1,3,4-thiadiazole-2-sulfonamides. Reaction of 5-(beta-aminoethylcarboxamido)-1,3,4-thiadiazole-2-sulfonamide with sulfonyl halides or acyl halides afforded a series of compounds possessing beta-alkyl/arylsulfonyl/carbonylamidoethylcarboxamido moieties in the 5 position of the thiadiazole-2-sulfonamide ring. The new derivatives were efficient inhibitors of three carbonic anhydrase (CA) isozymes, CA I, II (cytosolic forms) and IV (membrane-bound form), but especially against CA II and CA IV (in nanomolar range), the two isozymes known to play an important role in aqueous humor secretion within the ciliary processes of the eye. Some of the synthesized inhibitors possessed good water solubility (as hydrochlorides or sodium salts) and were applied as 2% solutions directly into the eye of normotensive or glaucomatous albino rabbits. Very strong intraocular pressure (IOP) lowering was observed for many of them for prolonged periods of 1-2 h, and the active drug was detected in eye tissues and fluids indicating that the antiglaucoma effect is due to CA inhibition within the eye.","PeriodicalId":15776,"journal":{"name":"Journal of enzyme inhibition","volume":"29 1","pages":"23-46"},"PeriodicalIF":0.0,"publicationDate":"1999-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87803060","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: 35

Synthesis and Mechanism of Action of Novel Thiocarbamate Inhibitors of Human Leukocyte Elastase. 新型人白细胞弹性酶硫氨基甲酸酯抑制剂的合成及作用机制研究。

Journal of enzyme inhibition Pub Date : 1999-11-01 DOI: 10.1080/14756369909030341

Sky Li-Pan Z, Joshi, Digenis

引用次数: 2

Interaction of Pig Kidney and Lentil Seedling Copper-Containing Amine Oxidases with Guanidinium Compounds. 猪肾和小扁豆幼苗含铜胺氧化酶与胍类化合物的相互作用。

Journal of enzyme inhibition Pub Date : 1999-11-01 DOI: 10.1080/14756369909030343

A. Padiglia, R. Medda, A. Lorrai, B. Murgia, J. Z. Pedersen, A. Agrò, G. Floris

引用次数: 5

A Kinetic Study on the Interaction between Tazobactam (A Penicillanic Acid Sulphone Derivative) and Active-Site Serine beta-Lactamases. 他唑巴坦(一种青霉酸磺基衍生物)与活性位点丝氨酸β -内酰胺酶相互作用动力学研究。

Journal of enzyme inhibition Pub Date : 1999-11-01

Perilli, Franceschini, Bonfiglio, Segatore, Stefani, Nicoletti, Tavio Perez Md, Bianchi, Zollo, Amicosante

引用次数: 0