Journal of Enzyme Inhibition and Medicinal Chemistry (J Enzym Inhib Med Chem )

Publisher: Taylor & Francis


The Journal of Enzyme Inhibition and Medicinal Chemistry is an international and interdisciplinary vehicle publishing new knowledge and findings on enzyme inhibitors and inhibitory processes. The journal publishes research papers, short communications and reviews on current developments across the disciplines of enzymology, cell biology, microbiology, physiology, pharmacology, drug design and biophysics. Among the various fields of enquiry, special attention is given to structural and molecular studies, kinetics and inactivation mechanisms, structure- activity relationships (including QSAR and graphic techniques) within a chemical series or group, drug development studies, and control mechanisms in metabolic processes.

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  • Website
    Journal of Enzyme Inhibition and Medicinal Chemistry website
  • Other titles
    Journal of enzyme inhibition and medicinal chemistry (Online), Enzyme inhibition and medicinal chemistry
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  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

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Taylor & Francis

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    • STM: Science, Technology and Medicine
    • SSH: Social Science and Humanities
    • 'Taylor & Francis (Psychology Press)' is an imprint of 'Taylor & Francis'
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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Inhibitory effects of some synthesized dihydroxycoumarin compounds on purified G6PD were investigated. For this purpose, initially human erythrocyte G6PD was purified 7069-fold in a yield of 33.6% by using ammonium sulfate precipitation and affinity chromatography which includes 2',5'-ADP Sepharose 4B. The purified enzyme showed a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Enzyme activity was determined spectrophotometrically according to Beutler method at 340 nm. 6,7-Dihydroxy-3-(2-methylphenyl)-2H-chromen-2-one (OPC), 6,7-dihydroxy-3-(3-methylphenyl)-2H-chromen-2-one (MPC) and 6,7-dihydroxy-3-(4-methylphenyl)-2H-chromen-2-one (PPC) were used as dihydroxycoumarin compounds. This study has demonstrated that G6PD activity is very highly sensitive to study coumarin derivatives.
    Journal of Enzyme Inhibition and Medicinal Chemistry 10/2014; 29(5):728–732.
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    ABSTRACT: Context: Mammary and placental 17β-hydroxysteroid dehydrogenase type 1 (17βHSD1). Objective: To assess the impact of testosterone, tibolone, and black cohosh on purified mammary and placental 17βHSD1. Materials and methods: 17βHSD1 was purified from human mammary gland and placenta by column chromatography, its activity was monitored by a radioactive activity assay, and the degree of purification was determined by gel electrophoresis. Photometric cofactor transformation analysis was performed to assess 17βHSD1 activity without or in presence of testosterone, tibolone and black cohosh. Results: 17βHSD1 from both sources displayed a comparable basal activity. Testosterone and tibolone metabolites inhibited purified mammary and placental 17βHSD1 activity to a different extent, whereas black cohosh had no impact. Discussion: Studies on purified enzymes reveal the individual action of drugs on local regulatory mechanisms thus helping to develop more targeted therapeutic intervention. Conclusion: Testosterone, tibolone and black cohosh display a beneficial effect on local mammary estrogen metabolism by not affecting or decreasing local estradiol exposure.
    Journal of Enzyme Inhibition and Medicinal Chemistry 08/2014;
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    ABSTRACT: Abstract A new affinity gel was synthesized for the purification of xanthine oxidase (XO, EC from bovine milk. The gel was prepared on a Sepharose 4B matrix on which a spacer arm based on l-tyrosine was covalently attached via CNBr activation, followed by reaction with the XO inhibitor p-aminobenzamidine. The elution conditions of affinity gel were determined at different pH values and ionic strengths. Maximum elution of XO was achieved at pH 9.0 and ionic strength around 0.4. The overall purification for XO was 1645-fold with 20.49% yield. SDS-PAGE of the enzyme indicates a single band with an apparent MW of 150 kDa. The gel provides a simple, rapid and effective useful for the purification of XO. Heat stability was determined on purified XO activity. Xanthine oxidase was preserved up to 70% with activity exposure of 60 °C and incubated for 60 min. These results indicated that the enzyme was heat stable.
    Journal of Enzyme Inhibition and Medicinal Chemistry 08/2014;
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    ABSTRACT: Abstract Context: Glycogen synthase kinase-3 (GSK-3) overactivity was correlated with several pathologies including type 2 diabetes mellitus, Alzheimer's disease, cancer, inflammation, obesity, etc. Objective: The aim of the current investigation was to model the inhibitory activity of maleimide derivatives - inhibitors of GSK-3, to evaluate the impact of alignment on statistical performances of the Quantitative Structure--Activity Relationship (QSAR) and the effect of the template on shape-similarity - binding affinity relationship. Materials and methods: Dragon descriptors were used to generate Projection to Latent Structures (PLS) models in order to identify the structural prerequisites of maleimides to inhibit GSK-3. Additionally, shape/volume structural analysis of binding site interactions was evaluated. Results: Reliable statistics [Formula: see text] = 0.938/0.920, [Formula: see text] = 0.866/0.838 for aligned and alignment free QSAR models and significant (Pearson, Kendall and Spearman) correlations between shape/volume similarity and affinities were obtained. Discussion and conclusions: The crucial structural features modulating the activity of maleimides include topology, charge, geometry, 2D autocorrelations, 3D-MoRSE as well as shape/volume and molecular flexibility.
    Journal of Enzyme Inhibition and Medicinal Chemistry 08/2014; 29(4):599-610.
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    ABSTRACT: Abstract All proteolytic enzymes, which are able to renature and reacquire the proteolytic activity on a copolymerized substrate, can be analyzed by zymography upon removal of sodium dodecyl sulfate (SDS). Protonography, the new technique described in this study, unlike zymography, allows the detection of a different protein, not a protease, i.e. of the carbonic anhydrase (CA, EC activity on a SDS polyacrylamide gel electrophoresis gel. CAs are zinc-containing enzymes that catalyze the reversible conversion of carbon dioxide to bicarbonate and protons. Hydrogen ions produced during the catalyzed reaction are responsible for the change of color that appears on the gel around the CA band. For this reason, we named the new technique "protonography". The following four salient features characterize this new technique: (a) on the basis of molecular weight markers, recombinant or native CAs with different molecular weights can be detected and quantified rapidly on a single gel; (b) the hydratase activity can be reversibly inhibited by SDS during electrophoresis and recovered by incubating the gel in aqueous Triton X-100; (c) it is possible to separate active oligomeric forms of CAs on the gel enabling their activities to be determined independently of one another. This feature is not possible when using solution assays; and (d) it can be a useful tool to establish if a putative or a newly identified CA in a genome is expressed and enzymatically active. This article outlines the general principles employed in protonography, providing an easy procedure to implement it in laboratories working with CAs. It also presents an overview of its development and current research applications through specific examples.
    Journal of Enzyme Inhibition and Medicinal Chemistry 07/2014;
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    ABSTRACT: Abstract In this preliminary study, a new series of some cerium vanadate derivatives have been investigated as new type of inhibitors of xanthine oxidase (XO; E.C XO is a superoxide-producing enzyme found normally in serum and the lungs, and its activity is concerned with several important health problems such as gout, severe liver damage, vascular dysfunction and injury, oxidative eye injury and renal failure. In this study, we present a critical overview of the effects of these novel type agents on XO with comparing the efficacy and safety profiles of allopurinol, the efficient classical inhibitor of XO.
    Journal of Enzyme Inhibition and Medicinal Chemistry 06/2014;
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    ABSTRACT: Abstract A series of new oxoaporphine derivatives were synthesized and their inhibitory activity of topoisomerase I, cytotoxicity and DNA-binding properties were studied. Oxoaporphine can strongly inhibit topoisomerase I at concentrations of 5-50 µM and the cytotoxicity of the derivatives are more potent than their lead compound. Hypochromism, broadening and red shift in the absorption spectra were observed when these compounds bind to calf thymus DNA (CT DNA). These spectral characteristics were consistent with the intercalative binding of these compounds.
    Journal of Enzyme Inhibition and Medicinal Chemistry 06/2014;
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    ABSTRACT: Abstract Falcipain-2 (FP-2) is a key cysteine protease from the malaria parasite Plasmodium falciparum. Many previous studies have identified FP-2 inhibitors; however, none has yet met the criteria for an antimalarial drug candidate. In this work, we assayed an in-house library of non-peptidic organic compounds, including (E)-chalcones, (E)-N'-benzylidene-benzohydrazides and alkyl-esters of gallic acid, and assessed the activity toward FP-2 and their mechanisms of inhibition. The (E)-chalcones 48, 54 and 66 showed the lowest IC50 values (8.5 ± 0.8 µM, 9.5 ± 0.2 µM and 4.9 ± 1.3 µM, respectively). The best inhibitor (compound 66) demonstrated non-competitive inhibition, and using mass spectrometry and fluorescence spectroscopy assays, we suggest a potential allosteric site for the interaction of this compound, located between the catalytic site and the hemoglobin binding arm in FP-2. We combined structural biology tools and mass spectrometry to characterize the inhibition mechanisms of novel compounds targeting FP-2.
    Journal of Enzyme Inhibition and Medicinal Chemistry 06/2014;
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    ABSTRACT: Abstract Stochastic sensing was employed for pattern recognition of HER-1 in biological fluids. Nanostructured materials such as 5,10,15,20-tetraphenyl-21H,23H-porphyrin, maltodextrin and α-cyclodextrin were used to modify diamond paste for stochastic sensing of HER-1. Pattern recognition of HER-1 in biological fluids was performed in a linear concentration range between 5.60 × 10(-11) and 9.72 × 10(-7 )mg ml(-1). The lower limits of determination (10(-12 )mg ml(-1) magnitude order) were recorded when maltodextrin and α-cyclodextrin were used for stochastic sensing. The pattern recognition test of HER-1 in biological fluids samples shows high reliability for both qualitative and quantitative assay.
    Journal of Enzyme Inhibition and Medicinal Chemistry 06/2014;
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    ABSTRACT: Abstract In a quest for developing novel anti-tubercular agents, a series of 3-benzylidene-4-chromanones 1a-l were evaluated for growth inhibition of Mycobacterium tuberculosis H37Rv. Three promising compounds 1d, g, j emerged as the lead compounds with the IC50 and IC90 values of less than 1 µg/mL. Evaluation of the potent compounds 1d, g, j and k against Vero monkey kidney cells revealed that these compounds are far more toxic to M. tuberculosis than to Vero cells. Structure-activity relationships demonstrated that 3-benzylidene-4-chromanones are more potent against M. tuberculosis than the related 2-benzylidene cycloalkanones and the meta substituted chromanone derivatives are more active than their ortho- and para-counterparts. Some guidelines for amplifying the project are presented.
    Journal of Enzyme Inhibition and Medicinal Chemistry 06/2014;
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    ABSTRACT: Abstract New class of FGFR1 kinase inhibitors with naphthostyril heterocycle has been identified. A series of N-phenylnaphthostyril-1-sulfonamides has been synthesized and tested in vitro. It was revealed that the most active compound N-(4-hydroxyphenyl)naphthostyril-1-sulfonamide inhibited FGFR1 with IC50 of 2 µM. In our preliminary studies, N-phenylnaphthostyril-1-sulfonamides demonstrated selectivity of FGFR1 inhibition and antiproliferative activity on cancer cell line. N-phenylnaphthostyril-1-sulfonamides have a good potential for further development as anticancer agents.
    Journal of Enzyme Inhibition and Medicinal Chemistry 06/2014;
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    ABSTRACT: Abstract The acetylcholinesterase inhibitory and/or antitumour activities of amino-, thio- and ester-derivatives of avarol selected were evaluated for the first time at in vitro conditions. Avarol-3',4'-dithioglycol (1) and avarol-4'-(3)mercaptopropionic acid (3) were shown to be the best inhibitors of the enzyme tested (0.50 µg and IC50 0.05 mM and 0.50 µg and IC50 0.12 mM, respectively), while 4'-tryptamine-avarone (9) and avarol-3'-(3)mercaptopropionic acid (2) exhibited the highest cytotoxicity against the human breast T-47D cancer cell line (IC50 0.66 µg/mL and 1.25 µg/mL, respectively). According to experimental data obtained, the sesquiterpenoid hydroquinone structure of bioactive avarol derivatives may inspire development of new pharmacologically useful substances to be used in the treatment of Alzheimer's disease and/or human breast tumour.
    Journal of Enzyme Inhibition and Medicinal Chemistry 06/2014;
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    ABSTRACT: Abstract Previously, a glycoglycerolipid isolated from marine algae was reported to be a potent and selective inhibitor of the human Myt1 kinase, an enzyme involved in cell cycle regulation with great potential as an anti-cancer target. Based on that report, a lot of research effort has been invested by several working groups to synthesize and derivatize this compound. However, reliable assay data confirming the inhibitory potential and the mechanism of action of these glycoglycerolipids are missing so far. Here, based on experimental data and theoretical considerations, we show that the aforesaid glycoglycerolipid 1,2-dipalmitoyl-3-(N-palmitoyl-6'-amino-6'-deoxy-α-d-glucosyl)-sn-glycerol is not an inhibitor of the human Myt1 kinase.
    Journal of Enzyme Inhibition and Medicinal Chemistry 06/2014;
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    ABSTRACT: Abstract Many cancer cells have high expression of ornithine decarboxylase (ODC) and there is a concerted effort to seek new inhibitors of this enzyme. The aim of the study was to initially characterize the inhibition properties, then to evaluate the cytotoxicity/antiproliferative cell based activity of N-ω-chloroacetyl-l-ornithine (NCAO) on three human cancer cell lines. Results showed NCAO to be a reversible competitive ODC inhibitor (Ki = 59 µM) with cytotoxic and antiproliferative effects, which were concentration- and time-dependent. The EC50,72h of NCAO was 15.8, 17.5 and 10.1 µM for HeLa, MCF-7 and HepG2 cells, respectively. NCAO at 500 µM completely inhibited growth of all cancer cells at 48 h treatment, with almost no effect on normal cells. Putrescine reversed NCAO effects on MCF-7 and HeLa cells, indicating that this antiproliferative activity is due to ODC inhibition.
    Journal of Enzyme Inhibition and Medicinal Chemistry 06/2014;
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    ABSTRACT: Abstract A new affinity gel was synthesized for the purification of carbonic anhydrase (CA, EC isozymes from erythrocytes. The gel was prepared on a Sepharose 4B matrix on which a spacer arm based on ethylenediamine was covalently attached via CNBr activation, followed by reaction with the CA inhibitor 4-isothiocyanato-benzenesulfonamide. The derivatized gel incorporated thioureido-benzenesulfonamide moieties as CA ligand. The binding capacity of the new affinity gel was determined at different temperatures, pH values, ionic strengths and elution buffers. The maximum binding of various CAs was achieved at 25 °C with pH 8.5 and ionic strength around 0.4. The overall purifications for human (h) hCA I and hCA II were 672- and 580-fold, and with 62 and 43% yields, respectively. SDS-polyacrylamide gel electrophoresis showed single bands for each purified isozymes, corresponding to a molecular weight of approx. 29 kDa. This is an easily obtainable, efficient and robust affinity gel, useful for the purification of many other α-CAs.
    Journal of Enzyme Inhibition and Medicinal Chemistry 06/2014;
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    ABSTRACT: Abstract Certain new 3H-quinazolin-4-one Schiff's bases were synthesized and screened for their activities against ulcerative colitis "UC". Their activity against phospholipase A2 and protease enzymes was also investigated. Some compounds possessed remarkable effect with different potentials against acetic acid-induced colitis model in rats. Compound 14 (50 mg/kg) was more effective than dexamesathone (0.01 mg/kg). It produced 79.78% protection of control colitis; however, compound 13 produced 75.80% protection and was considered as effective as dexamesathone with 75.30% protection. The observed results could be explained partially by their anti-inflammatory activities which appear as phospholipase A2 (hGIIA) and/or through protease inhibitor potentials. However, all the compounds under test showed preferential inhibition towards hG-IIA type of PLA2 rather than DrG-IB with varying degrees. Interestingly, compounds 14, 13, 12 and 11 displayed excellent inhibitory activity against phospholipase A2 accompanied by protease inhibitory profile.
    Journal of Enzyme Inhibition and Medicinal Chemistry 06/2014;