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

Publisher: Taylor & Francis

Journal description

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.

Current impact factor: 1.50

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2011 Impact Factor 1.617

Additional details

5-year impact 1.43
Cited half-life 5.00
Immediacy index 0.52
Eigenfactor 0.00
Article influence 0.27
Website Journal of Enzyme Inhibition and Medicinal Chemistry website
Other titles Journal of enzyme inhibition and medicinal chemistry (Online), Enzyme inhibition and medicinal chemistry
ISSN 1475-6374
OCLC 50446834
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Taylor & Francis

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Some individual journals may have policies prohibiting pre-print archiving
    • On author's personal website or departmental website immediately
    • On institutional repository or subject-based repository after either 12 months embargo for STM, Behavioural Science and Public Health Journals or 18 months embargo for SSH journals
    • Publisher's version/PDF cannot be used
    • On a non-profit server
    • Published source must be acknowledged
    • Must link to publisher version
    • Set statements to accompany deposits (see policy)
    • The publisher will deposit in on behalf of authors to a designated institutional repository including PubMed Central, where a deposit agreement exists with the repository
    • STM: Science, Technology and Medicine
    • SSH: Social Science and Humanities
    • Publisher last contacted on 25/03/2014
    • 'Taylor & Francis (Psychology Press)' is an imprint of 'Taylor & Francis'
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Carbonic anhydrases (CAs, EC 4.2.1.1) had six genetically distinct families described to date in various organisms. There are 16 known CA isoforms in humans. Human CA isoenzymes I and II (hCA I and hCA II) are ubiquitous cytosolic isoforms. Acetylcholine esterase (AChE. EC 3.1.1.7) is a hydrolase that hydrolyzes the neurotransmitter acetylcholine relaying the signal from the nerve. In this study, some trimethoxyindane derivatives were investigated as inhibitors against the cytosolic hCA I and II isoenzymes, and AChE enzyme. Both hCA isozymes were inhibited by trimethoxyindane derivatives in the low nanomolar range. These compounds were good hCA I inhibitors (Kis in the range of 1.66-4.14 nM) and hCA II inhibitors (Kis of 1.37-3.12 nM) and perfect AChE inhibitors (Kis in the range of 1.87-7.53 nM) compared to acetazolamide as CA inhibitor (Ki: 6.76 nM for hCA I and Ki: 5.85 nM for hCA II) and Tacrine as AChE inhibitor (Ki: 7.64 nM).
    Journal of Enzyme Inhibition and Medicinal Chemistry 02/2015;
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    ABSTRACT: Abstract In this study, the compounds having acrylophenone structure, 1-aryl-2-(N-methylpiperazinomethyl)-2-propen-1-one dihydrochlorides, were synthesized and their chemical structures were identified with (1)H NMR, (13)C NMR and HRMS spectra. The cytotoxicities of the compounds were tested towards Ca9-22 (human gingival carcinoma), HSC-2 (human oral squamous carcinoma), HSC-3 (human oral squamous carcinoma) and HSC-4 (human oral squamous carcinoma) cell lines as tumor cell lines and HGF (gingival fibroblasts), HPLF (periodontal ligament fibroblasts) and HPC (pulp cells) cell lines as non-tumor cell lines. PSE of the compound TA2, which has a methyl substituent on phenyl ring, pointed out the compound TA2 as a leader compound to be considered.
    Journal of Enzyme Inhibition and Medicinal Chemistry 02/2015;
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    ABSTRACT: Abstract We describe the characterisation of a series of 4,4'-biphenylsulfonamides as selective inhibitors of matrix metalloproteases MMP-2 and -13, two enzymes involved in cell invasion and angiogenesis. Double-inhibitor studies in the presence of acetohydroxamic acid show that these molecules do not bind the catalytic zinc. Moreover, two of the characterised inhibitors (11 and 19) act as non-competitive inhibitors, whereas the para-methyl ester derivative 13 behaves as a competitive inhibitor. This finding suggests that this class of molecules binds to a catalytic subsite, possibly the S1'-pocket. Moreover, since these compounds also act as inhibitors of carbonic anhydrases (CAs), another family of enzymes involved in cell invasion, they could be potentially useful as CA/MMP dual target inhibitors with increased efficacy as anticancer agents.
    Journal of Enzyme Inhibition and Medicinal Chemistry 02/2015;
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    ABSTRACT: Abstract In our continuing search for biologically active natural product(s) of plant origin, Buddleja saligna, a South African medicinal plant, was screened in line with its traditional use for antidiabetic (yeast alpha glucosidase inhibitory) and antiplasmodial (against a chloroquine sensitive strain of Plasmodium falciparum (NF54)) activities. The hexane fraction showed the most promising activity with regards to its antidiabetic (IC50 = 260 ± 0.112 µg/ml) and antiplasmodial (IC50 = 8.5 ± 1.6 µg/ml) activities. Using activity guided fractionation three known terpenoids (betulonic acid, betulone and spinasterol) were isolated from this species for the first time. The compounds displayed varying levels of biological activities (antidiabetic: 27.31 µg/ml ≥ IC50 ≥ 5.6 µg/ml; antiplasmodial: 14 µg/ml ≥ IC50 ≥ 2 µg/ml) with very minimal toxicity.
    Journal of Enzyme Inhibition and Medicinal Chemistry 02/2015;
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    ABSTRACT: Abstract The enzyme type 5 17β-hydroxysteroid dehydrogenase 5 (17β-HSD5) catalyzes the transformation of androstenedione (4-dione) to testosterone (T) in the prostate. This metabolic pathway remains active in cancer patients receiving androgen deprivation therapy. Since physicians seek to develop advantageous and better new treatments to increase the average survival of these patients, we synthesized several different dehydroepiandrosterone derivatives. These compounds have a pyrazole or imidazole function at C-17 and an ester moiety at C-3 and were studied as inhibitors of 17β-HSD5. The kinetic parameters of this enzyme were determined for use in inhibition assays. Their pharmacological effect was also determined on gonadectomized hamsters treated with Δ(4)-androstenedione (4-dione) or testosterone (T) and/or the novel compounds. The results indicated that the incorporation of a heterocycle at C-17 induced strong 17β-HSD5 inhibition. These derivatives decreased flank organ diameter and prostate weight in castrated hamsters treated with T or 4-dione. Inhibition of 17β-HSD5 by these compounds could have therapeutic potential for the treatment of prostate cancer and benign prostatic hyperplasia.
    Journal of Enzyme Inhibition and Medicinal Chemistry 02/2015;
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    ABSTRACT: Abstract Tyrosinase plays a pivotal role in the synthesis of melanin pigment synthesis on skin utilizing tyrosine as a substrate. Melanin is responsible for the protection against harmful ultraviolet irradiation, which can cause significant pathological conditions, such as skin cancers. However, it can also create esthetic problems when accumulated as hyperpigmented spots. Various skin-whitening ingredients which inhibit tyrosinase activity have been identified. Some of them, especially ones with natural product origins, possess phenolic moiety and have been employed in cosmetic products. Semi-synthetic and synthetic inhibitors have also been developed under inspiration of the natural inhibitors yet some of which have no phenolic groups. In this review, tyrosinase inhibitors with natural, semi-synthetic and synthetic origins are listed up with their structures, activities and characteristics. Further, a recent report on the adverse effect of a natural melanin synthesis inhibitor which was included in skin-whitening cosmetics is also briefly discussed.
    Journal of Enzyme Inhibition and Medicinal Chemistry 02/2015;
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    ABSTRACT: Abstract A new and specific HPLC-DAD method for the direct determination of Prulifloxacin and its active metabolite, Ulifloxacin, in human plasma has been developed. Plasma samples were analysed after a simple solid phase extraction (SPE) clean-up using a new HILIC stationary phase based high-performance liquid chromatography (HPLC) column and an ammonium acetate buffer (5 mM, pH 5.8)/acetonitrile (both with 1% Et3N, v/v) mobile phase in isocratic elution mode, with Danofloxacin as the internal standard. Detection was performed using DAD from 200 to 500 nm and quantitative analyses were carried out at 278 nm. The LOQ of the method was 1 μg/mL of the cited analytes and the calibration curve showed a good linearity up to 25 μg/mL. For both analytes the precision (RSD%) and the trueness (bias%) of the method fulfil with International Guidelines. The method was applied for stability studies, at three QC concentration levels, in human plasma samples stored at different temperature of + 25, + 4 and -20 °C in order to evaluate plasma stability profiles.
    Journal of Enzyme Inhibition and Medicinal Chemistry 02/2015;
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    ABSTRACT: Abstract Two viral proteases of severe acute respiratory syndrome coronavirus (SARS-CoV), a chymotrypsin-like protease (3CL(pro)) and a papain-like protease (PL(pro)) are attractive targets for the development of anti-SARS drugs. In this study, nine alkylated chalcones (1-9) and four coumarins (10-13) were isolated from Angelica keiskei, and the inhibitory activities of these constituents against SARS-CoV proteases (3CL(pro) and PL(pro)) were determined (cell-free/based). Of the isolated alkylated chalcones, chalcone 6, containing the perhydroxyl group, exhibited the most potent 3CL(pro) and PL(pro) inhibitory activity with IC50 values of 11.4 and 1.2 µM. Our detailed protein-inhibitor mechanistic analysis of these species indicated that the chalcones exhibited competitive inhibition characteristics to the SARS-CoV 3CL(pro), whereas noncompetitive inhibition was observed with the SARS-CoV PL(pro).
    Journal of Enzyme Inhibition and Medicinal Chemistry 02/2015;
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    ABSTRACT: Abstract The aims of this study were to examine the antiproliferation of Humulus lupulus extracts on human hepatoma carcinoma (Hep3B) and human colon carcinoma (HT-29) cell lines along with enzyme inhibitory effects of the crude extracts. Potential cell cytotoxicity of six different H. lupulus extracts were assayed on various cancer cells using MTT assay at 24, 48 and 72 h intervals. Methanol-1 extract has inhibited the cell proliferation with doses of 0.6-1 mg/mL in a time dependent (48 and 72 hours) manner in Hep3B cells with 70% inhibition, while inhibitory effect was not seen in colon cancer cells. Acetone extract has increased the cell proliferation at low doses of 0.1 mg/mL for 72 h in Hep3B cells and 0.1-0.2 mg/mL for 48 and 72 h in HT29 cells. The inhibitory effects of the extracts were compared by relative maximum activity values (Vmax) using proteases such as α-chymotrypsin, trypsin and papain, tyrosinase and β-lactamase (penicillinase).
    Journal of Enzyme Inhibition and Medicinal Chemistry 02/2015;
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    ABSTRACT: Abstract A series of 5,7-dimethyl-oxazolo[5,4-d]pyrimidine-4,6(5H,7H)-dione derivatives, N5a-5l, was designed, synthesized and evaluated for their FGFR1-inhibition ability as well as cytotoxicity against three cancer cell lines (H460, B16F10 and A549) in vitro. Several compounds displayed good-to-excellent potency against these cancer cell lines compared to SU5402. Structure-activity relationship analyses indicated that compounds with a rigid structure and more heteroatoms at the side chain of the parent ring were more effective than those without these substitutions. The compound N5g (37.4% FGFR1 inhibition at 1.0 μM) was identified to have the most potent antitumor activities, with IC50 values of 5.472, 4.260 and 5.837 μM against H460, B16F10 and A549 cell lines, respectively. Together, our results suggest that 5,7-dimethyl-oxazolo[5,4-d]pyrimidine-4,6(5H,7H)-dione derivatives may serve as potential agents for the treatment of FGFR1-mediated cancers.
    Journal of Enzyme Inhibition and Medicinal Chemistry 02/2015;
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    ABSTRACT: Abstract Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze a simple reaction in all life domains: the carbon dioxide hydration to bicarbonate and protons: CO2 + H2O → [Formula: see text] + H(+). Six different, genetically distinct CA families are known to date, the α-, β-, γ-, δ-, ζ- and η-CAs. Bacteria encode for CAs belong to the α-, β- and γ-classes. Recently, our groups investigated the presence of CAs in two bacteria belonging to the genus Sulfurihydrogenibium living in hot springs all over the world, at temperatures of up to 110 °C. The α-CAs from Sulfurihydrogenibium yellowstonense and Sulfurihydrogenibium azorense, denominated SspCA and SazCA, respectively, are highly thermostable, maintaining a good catalytic activity even after being heated for a prolonged period. Moreover, SazCA was to be the fastest CA known to date with a kcat value of 4.40 × 10(6) s(-1) and a kcat/KM value of 3.5 × 10(8) M(-1) s(-1). SspCA also showed a good catalytic activity for the same reaction, with a kcat value of 9.35 × 10(5) s(-1) and a kcat/KM value of 1.1 × 10(8) M(-1) s(-1), proving that the "extremo-α-CAs" are between the most effective CAs known to date. Here, we describe a failed tentative to obtain a super-CA, SupCA, by combining the amino acid sequence of SazCA and SspCA. To achieve this goal we introduced six His residues in N-terminal sequence of SspCA. However the obtained SupCA showed lower catalytic activity and thermostability compared to both extremophilic enzymes from which it has been designed. We rationalized the biochemical reasons of this failure, which may be useful to design enzymes with a better catalytic activity.
    Journal of Enzyme Inhibition and Medicinal Chemistry 02/2015;
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    ABSTRACT: Abstract 4-Chloro-3-({[(substitutedamino)carbonothioyl]amino}sulfonyl)-N-(2-methyl-2,3-dihydro-1H-indole-1-yl)benzamide (1-20) and 4-chloro-3-({[3-(substituted)-4-oxo-1,3-thiazolidine-2-ylidene]amino}sulfonyl)-N-(2-methyl-2,3-dihydro-1H-indole-1-yl)benzamide derivatives (21-31) were synthesized from 4-chloro-N-(2-methyl-2,3-dihydroindol-1-yl)-3-sulfamoylbenzamide (indapamide). 4-Chloro-3-({[(4-chlorophenyl) amino) carbonothioyl]amino}sulfonyl)-N-(2-methyl-2,3-dihydro-1H-indole-1-yl)benzamide 12 demonstrated the highest proapoptotic activity among all synthesized compounds on melanoma cell lines MDA-MB-435 with 3.7% growth inhibition at the concentration of 10 µM. Compound 12 (SGK 266) was evaluated in vitro using the MTT colorimetric method against melanoma cancer cell line MDA-MB435 growth inhibition for different doses and exhibited anticancer activity with IC50 values of 85-95 µM against melanoma cancer cell line MDA-MB435. In addition, this compound was investigated as inhibitors of four physiologically relevant human carbonic anhydrase isoforms, hCA I, II, IX and XII. The compund inhibited these enzymes with IC50 values ranging between 0.72 and 1.60 µM.
    Journal of Enzyme Inhibition and Medicinal Chemistry 02/2015;
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    ABSTRACT: Abstract Protonography, a sodium dodecyl sulfate - polyacrylamide gel electrophoresis (SDS-PAGE) technique derived from zymography was recently reported by our group to be an effective, cheap and reproducible technique for evidencing catalytically active α-carbonic anhydrase (CA, EC 4.2.1.1) isoforms, such as the bovine red blood cell isoform bCA or the bacterial enzyme from Vibrio cholerae, VchCA. CA activity was also observed on the protonogram of a cellular extract of Escherichia coli, evidencing the presence of one or more β-class such enzymes. Here we show that protonography can also be applied to the recently discovered η-CA family using the Plasmodium falciparum enzyme PfCA as an example. The protonogram of PfCA clearly showed catalytically active η-CA with a specific band at 22.0 kDa, which was quite distinct from the band of the red blood cell bovine enzyme bCA, which was observed at 28.8 kDa. The different migration pattern of α- and η-CAs might be a useful tool to detect Plasmodium falciparum in infected human red blood cells by an easy, routine inexpensive technique.
    Journal of Enzyme Inhibition and Medicinal Chemistry 02/2015;
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    ABSTRACT: Abstract Arachidonic acid is an unsaturated fatty acid liberated from phospholipids of cell membranes. NSAIDs are known as targets of cyclooxygenase enzyme (COX-1, COX-2 and COX-3) in arachidonic acid metabolism. This mechanism of COX-2 in carcinogenesis causes cancer. In addition, COX-2 plays a role in the early stages of hepatocarcinogenesis. Hepatitis C virus (HCV) infection is cause of liver cirrhosis and hepatocellular carcinoma (HCC). The aim of our study was to improve effective agents against HCV. A novel series of new etodolac 1,2,4-triazoles derivatives (4a-h) have been synthesized and investigated for their activity against HCV NS5B polymerase. Compound 4a was found to be the most active with IC50 value of 14.8 µM. In accordance with these results, compound 4a was screened for anti-cancer activity on liver cancer cell lines (Huh7, Mahlavu, HepG2, FOCUS). Compound 4a showed anti-cancer activity against Huh7 human hepatoma cell line with IC50 value of 4.29 µM. Therefore, compound 4a could be considered as a new anti-cancer and anti-HCV lead compound.
    Journal of Enzyme Inhibition and Medicinal Chemistry 02/2015;
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    ABSTRACT: Abstract A series of hydroxy and phenolic compounds have been assayed for the inhibition of two physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isozymes, the cytosolic human isozymes I and II. The investigated molecules showed inhibition constants in the range of 1.07-4003 and 0.09-31.5 μM at the hCA I and hCA II enzymes, respectively. In order to investigate the binding mechanisms of these inhibitors, in silico studies were also applied. Molecular docking scores of the studied compounds are compared using three different scoring algorithms, namely Glide/SP, Glide/XP and Glide/IFD. In addition, different ADME (absorption, distribution, metabolism and excretion) analysis was performed. All the examined compounds were found within the acceptable range of pharmacokinetic profiles.
    Journal of Enzyme Inhibition and Medicinal Chemistry 02/2015;
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    ABSTRACT: Abstract Hericium erinaceum is an edible and medicinal mushroom widely used in Korea, Japan, and China. On the search for biologically active compounds supporting the medicinal usage, the MeOH extract of the fruiting bodies of H. erinaceum was investigated for its chemical constituents. Six compounds were isolated and identified as hericenone D (1), (22E,24R)-5α,8α-epidioxyergosta-6,22-dien-3β-ol (2), erinacerin B (3), hericenone E (4), hericenone F (5) and isohericerin (6) by comparing their spectroscopic data with previously reported values. The inhibitory effects on adriamycin-induced cellular senescence in human dermal fibroblasts (HDFs) and human umbilical vein endothelial cells (HUVECs) of the isolates (1-6) were studied. Among the isolated compounds, ergosterol peroxide (2) reduced senescence associated β-galactosidase (SA-β-gal) activity increased in HUVECs treated with adriamycin. According to experimental data obtained, the active compound may inspire the development of a new pharmacologically useful substance to be used in the treatment and prevention of age-related diseases.
    Journal of Enzyme Inhibition and Medicinal Chemistry 02/2015;
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    ABSTRACT: Abstract A small series of C-glycosides containing the phenol moiety was tested for the inhibition of the β-class carbonic anhydrases (βCAs, EC 4.2.1.1) from Brucella suis. Many compounds showed activities in the micromolar or submicromolar range and excellent selectivity for pathogen CAs over human isozymes. Glycosides incorporating the 3-hydroxyphenyl moiety showed the best inhibition profile, and therefore this functionality represents lead for the development of novel anti-infectives with a new mechanism of action.
    Journal of Enzyme Inhibition and Medicinal Chemistry 02/2015;
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    ABSTRACT: Abstract 7-Amino-3,4-dihydro-1H-quinolin-2-one, a compound structurally similar to coumarins, recently discovered class of inhibitors of the α-carbonic anhydrases (CAs, EC 4.2.1.1) was investigated for its interaction with all human (h) CA isoforms, hCA I-XIV. The compound was not an inhibitor of the cytosolic, widespread isoform hCA II (KI > 10 µM), was a weak inhibitor of hCA I, III, IV, VA, VI and XIII (KIs in the range of 0.90-9.5 µM) but effectively inhibited the cytosolic isoform hCA VII (KI of 480 nM) as well as the transmembrane isoforms hCA IX, XII and XIV (KIs in the range of 16.1-510 nM). Against many CA isoforms this lactam was a better inhibitor compared to the structurally similar 4-methyl-7-aminocoumarin, but unlike this compound, the lactam ring was not hydrolyzed and the inhibition was due to the intact bicyclic amino-quinolinone scaffold. Bicyclic lactams strucurally related to coumarins are thus a new class of CA inhibitors possessing however a distinct inhibition mechanism compared to the coumarins which undergo a hydrolysis of their lactone ring for generating the enzyme inhibitory species.
    Journal of Enzyme Inhibition and Medicinal Chemistry 02/2015;