2,263 results match your criteria Journal of Enzyme Inhibition and Medicinal Chemistry [Journal]


Synthesis and biological evaluation of 3-arylcoumarins as potential anti-Alzheimer's disease agents.

J Enzyme Inhib Med Chem 2019 Dec;34(1):651-656

a School of Medicine and Life Sciences , University of Jinan-Shandong Academy of Medical Sciences , Jinan , China.

Alzheimer's disease, a neurodegenerative illness, has the extremely complex pathogenesis. Accumulating evidence indicates there is a close relationship between several enzymes and Alzheimer's disease. Various substituted 3-arylcoumarin derivatives were synthesised, and their in vitro activity, including cholinesterase inhibitory activity, monoamine oxidase inhibitory activity, and antioxidant activity were investigated. Read More

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http://dx.doi.org/10.1080/14756366.2019.1574297DOI Listing
December 2019

Design, synthesis, and biological evaluation of novel derivatives of dithiodiglycolic acid prepared via oxidative coupling of thiols.

J Enzyme Inhib Med Chem 2019 Dec;34(1):665-671

a Saint Petersburg State University , Saint Petersburg , Russian Federation.

Human thioredoxin reductase 1 (TrxR1) is a selenocysteine-containing enzyme which plays a crucial role in regulating numerous redox signalling pathways within the cell. While its functioning is important in all cells, levels of TrxR1 expression are higher in cancer cells, possibly as an adaptation to much higher levels of reactive oxygen species and the need for more extensive DNA synthesis. This makes TrxR1 an attractive target for cancer therapy development. Read More

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http://dx.doi.org/10.1080/14756366.2019.1575372DOI Listing
December 2019

(Hetero)aryl substituted thiazol-2,4-yl scaffold as human carbonic anhydrase I, II, VII and XIV activators.

J Enzyme Inhib Med Chem 2019 Dec;34(1):224-229

a Université de Lille, Inserm, CHU Lille, UMR-S 1172-JPArc-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer , Lille 59000 , France.

Using histamine as lead molecule, a library of (hetero)aryl substituted thiazol-2,4-yl derivatives incorporating pyridine as proton shuttling moiety were obtained and investigated as activators of human carbonic anhydrase (CA, EC 4.2.1. Read More

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http://dx.doi.org/10.1080/14756366.2018.1543292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327990PMC
December 2019

(E)-N'-Arylidene-2-(4-oxoquinazolin-4(3H)-yl) acetohydrazides: Synthesis and evaluation of antitumor cytotoxicity and caspase activation activity.

J Enzyme Inhib Med Chem 2019 Dec;34(1):465-478

a Pharmaceutical Chemistry , Hanoi University of Pharmacy , Hanoi , Vietnam.

In our search for novel small molecules activating procaspase-3, we have designed and synthesised a series of novel acetohydrazides incorporating quinazolin-4(3H)-ones (5, 6, 7). Biological evaluation revealed eight compounds with significant cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer). The most potent compound 5t displayed cytotoxicity up to 5-fold more potent than 5-FU. Read More

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http://dx.doi.org/10.1080/14756366.2018.1555536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338265PMC
December 2019

Hydroxyl-substituted double Schiff-base condensed 4-piperidone/cyclohexanones as potential anticancer agents with biological evaluation.

J Enzyme Inhib Med Chem 2019 Dec;34(1):264-271

a School of Basic Medical Sciences, Binzhou Medical University , Yantai , P. R. China.

Novel hydroxyl-substituted double Schiff-base 4-piperidone/cyclohexanone derivatives, 3a-e, 4a-e, 5a-d, and 6a-c, were synthesized and fully characterized by H NMR, IR and elemental analysis. The cytotoxicity against human carcinoma cell lines A549, SGC7901, HePG2, HeLa, K562, THP-1 and non-malignant LO2 cell lines were evaluated. The results showed 4-piperidinone derivatives displayed better cytotoxicity than cyclohexanone derivatives, especially for 3,4,5-trihydroxyphenyl-substituted BAP 5c. Read More

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http://dx.doi.org/10.1080/14756366.2018.1501042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327999PMC
December 2019

Discovery of cyanopyridine scaffold as novel indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors through virtual screening and preliminary hit optimisation.

J Enzyme Inhib Med Chem 2019 Dec;34(1):250-263

a State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Design and Optimization , China Pharmaceutical University , Nanjing , People's Republic of China.

With the aim of discovering novel IDO1 inhibitors, a combined similarity search and molecular docking approach was employed to the discovery of 32 hit compounds. Testing the screened hit compounds has led to several novel submicromolar inhibitors. Especially for compounds LVS-019 with cyanopyridine scaffold, showed good IDO1 inhibitory activity. Read More

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http://dx.doi.org/10.1080/14756366.2018.1480614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327983PMC
December 2019

Synthesis, molecular modelling and anticancer evaluation of new pyrrolo[1,2-b]pyridazine and pyrrolo[2,1-a]phthalazine derivatives.

J Enzyme Inhib Med Chem 2019 Dec;34(1):230-243

a Faculty of Chemistry , Alexandru Ioan Cuza University of Iasi , Iasi , Romania.

Two new series of heterocyclic derivatives with potential anticancer activity, in which a pyrrolo[1,2-b]pyridazine or a pyrrolo[2,1-a]phthalazine moiety was introduced in place of the 3'-hydroxy-4'-methoxyphenyl ring of phenstatin have been synthesised and their structure-activity relationship (SAR) was studied. Fourteen of the new compounds were evaluated for their in vitro cytotoxic activity by National Cancer Institute (NCI) against 60 human tumour cell lines panel. The best five compounds in terms of in vitro growth inhibition were screened in the second stage five dose-response studies, three of them showing a very good antiproliferative activity with GI<100 nM on several cell lines including colon, ovarian, renal, prostate, brain and breast cancer, melanoma and leukemia. Read More

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http://dx.doi.org/10.1080/14756366.2018.1550085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327994PMC
December 2019
1 Read

Structure-guided design of anti-cancer ribonucleotide reductase inhibitors.

J Enzyme Inhib Med Chem 2019 Dec;34(1):438-450

a Department of Pharmacology, School of Medicine , Case Western Reserve University , Cleveland , OH , USA.

Ribonucleotide reductase (RR) catalyses the rate-limiting step of dNTP synthesis, establishing it as an important cancer target. While RR is traditionally inhibited by nucleoside-based antimetabolites, we recently discovered a naphthyl salicyl acyl hydrazone-based inhibitor (NSAH) that binds reversibly to the catalytic site (C-site). Here we report the synthesis and in vitro evaluation of 13 distinct compounds (TP1-13) with improved binding to hRR over NSAH (TP8), with lower K's and more predicted residue interactions. Read More

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http://dx.doi.org/10.1080/14756366.2018.1545226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328008PMC
December 2019

A comprehensive review on tyrosinase inhibitors.

J Enzyme Inhib Med Chem 2019 Dec;34(1):279-309

e Institute of Biochemistry and Biophysics, University of Tehran , Tehran , Iran.

Tyrosinase is a multi-copper enzyme which is widely distributed in different organisms and plays an important role in the melanogenesis and enzymatic browning. Therefore, its inhibitors can be attractive in cosmetics and medicinal industries as depigmentation agents and also in food and agriculture industries as antibrowning compounds. For this purpose, many natural, semi-synthetic and synthetic inhibitors have been developed by different screening methods to date. Read More

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http://dx.doi.org/10.1080/14756366.2018.1545767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327992PMC
December 2019
1 Read

Synthesis and biological evaluation of novel N-heterobivalent β-carbolines as angiogenesis inhibitors.

J Enzyme Inhib Med Chem 2019 Dec;34(1):375-387

a School of Chemistry and Chemical Engineering/Key Laboratory for Green Processing of Chemical Engineering of XinJiang Bingtuan , Shihezi University , Shihezi , China.

A series of novel N-heterobivalent β-carbolines has been synthesized. All the novel compounds were tested for their anticancer activity against six tumour cell lines in vitro. Among these molecules, compounds 5b, and 5w exhibited strong cytotoxic activities with IC value of lower than 20 μM. Read More

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http://dx.doi.org/10.1080/14756366.2018.1497619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327987PMC
December 2019
1 Read

New sulfonamides containing organometallic-acylhydrazones: synthesis, characterisation and biological evaluation as inhibitors of human carbonic anhydrases.

J Enzyme Inhib Med Chem 2019 Dec;34(1):451-458

b Dipartimento Neurofarba , Università degli Studi di Firenze , Firenze , Italy.

A series of organometallic acylhydrazones was prepared, incorporating Re(CO), Mn(CO) and ferrocenyl moieties, which were subsequently reacted with amino-sulfonamides in order to obtain carbonic anhydrase (CA, EC 4.2.1. Read More

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http://dx.doi.org/10.1080/14756366.2018.1555156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327986PMC
December 2019

Targeting Loxosceles spider Sphingomyelinase D with small-molecule inhibitors as a potential therapeutic approach for loxoscelism.

J Enzyme Inhib Med Chem 2019 Dec;34(1):310-321

a Immunochemistry Laboratory , Butantan Institute , São Paulo , SP , Brazil.

Loxosceles spiders' venoms consist of a mixture of proteins, including the sphingomyelinases D (SMases D), which are the main toxic components responsible for local and systemic effects in human envenomation. Herein, based on the structural information of SMase D from Loxosceles laeta spider venom and virtual docking-based screening approach, three benzene sulphonate compounds (named 1, 5 and 6) were identified as potential Loxosceles SMase D inhibitors. All compounds inhibited the hydrolysis of the sphingomyelin substrate by both recombinant and native SMases D. Read More

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http://dx.doi.org/10.1080/14756366.2018.1546698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327989PMC
December 2019

The chemical diversity and structure-based discovery of allosteric modulators for the PIF-pocket of protein kinase PDK1.

J Enzyme Inhib Med Chem 2019 Dec;34(1):361-374

a Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education , Shanghai Jiao Tong University, School of Medicine , Shanghai , China.

Phosphoinositide-dependent protein kinase-1 (PDK1) is an important protein in mediating the PI3K-AKT pathway and is thus identified as a promising target. The catalytic activity of PDK1 is tightly regulated by allosteric modulators, which bind to the PDK1 Interacting Fragment (PIF) pocket of the kinase domain that is topographically distinct from the orthosteric, ATP binding site. Allosteric modulators by attaching to the less conserved PIF-pocket have remarkable advantages such as higher selectivity, less side effect, and lower toxicity. Read More

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http://dx.doi.org/10.1080/14756366.2018.1553167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327997PMC
December 2019
2.383 Impact Factor

Inhibition of bacterial α-, β- and γ-class carbonic anhydrases with selenazoles incorporating benzenesulfonamide moieties.

J Enzyme Inhib Med Chem 2019 Dec;34(1):244-249

a Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche , Università degli Studi di Firenze , Florence , Italy.

A series of benzenesulfonamides incorporating selenazoles with diverse substitution patterns were investigated as inhibitors of six bacterial carbonic anhydrases (CAs, EC 4.2.1. Read More

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http://dx.doi.org/10.1080/14756366.2018.1547287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327980PMC
December 2019

Synthesis and biological evaluation of thiazole derivatives as LbSOD inhibitors.

J Enzyme Inhib Med Chem 2019 Dec;34(1):333-342

a Programa de pós-graduação em Biotecnologia , Universidade Estadual de Feira de Santana , Feira de Santana , BA , Brazil.

Leishmaniasis is considered as one of the major neglected tropical diseases due to its magnitude and wide geographic distribution. Leishmania braziliensis, responsible for cutaneous leishmaniasis, is the most prevalent species in Brazil. Superoxide dismutase (SOD) belongs to the antioxidant pathway of the parasites and human host. Read More

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http://dx.doi.org/10.1080/14756366.2018.1550752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327998PMC
December 2019

A mitochondrial-targeted peptide ameliorated podocyte apoptosis through a HOCl-alb-enhanced and mitochondria-dependent signalling pathway in diabetic rats and in vitro.

J Enzyme Inhib Med Chem 2019 Dec;34(1):394-404

c Special Medical Service Center, Zhujiang Hospital , Southern Medical University , Guangzhou , China.

Mitochondria play important roles in the development of diabetic kidney disease (DKD). The SS peptide is a tetrapeptide that is located and accumulated in the inner mitochondrial membrane; it reduces reactive oxygen species (ROS) and prevents mitochondrial dysfunction. Podocytes are key cellular components in DKD progression. Read More

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http://dx.doi.org/10.1080/14756366.2018.1488697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327984PMC
December 2019

A feature-based analysis identifies COL1A2 as a regulator in pancreatic cancer.

J Enzyme Inhib Med Chem 2019 Dec;34(1):420-428

a Department of Intervention Therapy , Second Affiliated Hospital of Dalian Medical University , Dalian , Liaoning , China.

This study aimed to identify genetic biomarkers in pancreatic cancer (PC) and explore its function in PC via a feature-base analysis of bioinformatics. OMIM and DisGeNET databases discovered 209 PC connected genes and then 516 connected genes were identified. We selected 29 genes according to optimal features and chose COL1A2, which had the highest expression, for the following experiment. Read More

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https://www.tandfonline.com/doi/full/10.1080/14756366.2018.1
Publisher Site
http://dx.doi.org/10.1080/14756366.2018.1484734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327995PMC
December 2019
2 Reads

Inhibition of acetylcholinesterase and butyrylcholinesterase with uracil derivatives: kinetic and computational studies.

J Enzyme Inhib Med Chem 2019 Dec;34(1):429-437

f Department of Agricultural Biotechnology , Agriculture Faculty, Ondokuz Mayis University , Samsun , Turkey.

Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) inhibitors are interesting compounds for different therapeutic applications, among which Alzheimer's disease. Here, we investigated the inhibition of these cholinesterases with uracil derivatives. The mechanism of inhibition of these enzymes was observed to be due to obstruction of the active site entrance by the inhibitors scaffold. Read More

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http://dx.doi.org/10.1080/14756366.2018.1543288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327988PMC
December 2019

Trypsin inhibitors: promising candidate satietogenic proteins as complementary treatment for obesity and metabolic disorders?

J Enzyme Inhib Med Chem 2019 Dec;34(1):405-419

a Department of Biochemistry, Biosciences Center, Federal University of Rio Grande do Norte , Natal , Brazil.

The increase in non-communicable chronic diseases has aroused interest in the research of adjuvants to the classic forms of treatments. Obesity and metabolic syndrome are the main targets of confrontation because they relate directly to other chronic diseases. In this context, trypsin inhibitors, molecules with wide heterologous application, appear as possibilities in the treatment of overweight and obesity due to the action on satiety related mechanisms, mainly in the modulation of satiety hormones, such as cholecystokinin. Read More

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http://dx.doi.org/10.1080/14756366.2018.1542387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327991PMC
December 2019

Organoruthenium(II) complexes of acetazolamide potently inhibit human carbonic anhydrase isoforms I, II, IX and XII.

J Enzyme Inhib Med Chem 2019 Dec;34(1):388-393

b Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche , Università degli Studi di Firenze , Florence , Italy.

Two acetazolamide (AAZ) complexes with ruthenium(II) η-p-cymene chloride were synthesised, characterised and tested for their inhibitory effects on several carbonic anhydrase (CA, EC 4.2.1. Read More

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http://dx.doi.org/10.1080/14756366.2018.1547288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327979PMC
December 2019

Prostate cancer cells and exosomes in acidic condition show increased carbonic anhydrase IX expression and activity.

J Enzyme Inhib Med Chem 2019 Dec;34(1):272-278

a Department of Oncology and Molecular Medicine , National Institute of Health , Rome , Italy.

Acidity and hypoxia are crucial phenotypes of tumour microenvironment both contributing to the selection of malignant cells under a micro evolutionistic pressure. During the tumour progression, nanovesicles, called exosomes and the metalloenzyme carbonic anhydrase IX (CA IX) affect the tumour growth and proliferation. Exosomes are released into the tumour microenvironment and spilt all over the body, while CA IX is a tumour-associated protein overexpressed in many different solid tumours. Read More

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http://dx.doi.org/10.1080/14756366.2018.1538980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327996PMC
December 2019

Do CO and oxidative stress induce cancer?: a brief study about the evaluation of PON 1, CAT, CA and XO enzyme levels on head and neck cancer patients.

J Enzyme Inhib Med Chem 2019 Dec;34(1):459-464

c Department of Medical Biology, Faculty of Medicine , Ankara Yildirim Beyazit University, Bilkent Campus , Ankara , Turkey.

Head and neck cancer (HNC) is one of the most common malignancies in the world. HNC is a group of cancers that starts in the mouth, nose, throat, larynx, sinuses, or salivary glands. According to this section of the body parts; induction of cancer can be associated with CO and oxidative stress. Read More

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http://dx.doi.org/10.1080/14756366.2018.1555157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327982PMC
December 2019
1 Read

Synthesis carbonic anhydrase enzyme inhibition and antioxidant activity of novel benzothiazole derivatives incorporating glycine, methionine, alanine, and phenylalanine moieties.

J Enzyme Inhib Med Chem 2019 Dec;34(1):343-349

c Dipartimento Neurofarba, Sezione Di Scienze Farmaceutiche E Nutraceutiche e Laboratorio Di Chimica Bioinorganica, Universita` Degli Studi Di Firenze , Florence , Italy.

Thirteen novel benzothiazole derivatives incorporating glycine, methionine, alanine, and phenylalanine were synthesised by facile acylation reactions through benzotriazole or DCC mediated reactions and their structures were identified by H-NMR, 13C-NMR, and FT-IR spectroscopic techniques and elemental analysis. The carbonic anhydrase (CA, EC 4.2. Read More

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http://dx.doi.org/10.1080/14756366.2018.1553040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327993PMC
December 2019
1 Read

Soyasaponins from Zolfino bean as aldose reductase differential inhibitors.

J Enzyme Inhib Med Chem 2019 Dec;34(1):350-360

a Department of Biology , University of Pisa , Pisa , Italy.

Seven triterpenoid saponins were identified in methanolic extracts of seeds of the Zolfino bean landrace (Phaseolus vulgaris L.) by HPLC fractionation, revealing their ability to inhibit highly purified human recombinant aldose reductase (hAKR1B1). Six of these compounds were associated by MS analysis with the following saponins already reported in different Phaseolus vulgaris varieties: soyasaponin Ba (V), soyasaponin Bb, soyasaponin Bd (sandosaponin A), soyasaponin αg, 3-O-[R-l-rhamnopyranosyl(1 → 2)-α-d-glucopyranosyl(1 → 2)-α-d-glucuronopyranosyl]olean-12-en-22-oxo-3α,-24-diol, and soyasaponin βg. Read More

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http://dx.doi.org/10.1080/14756366.2018.1553166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327985PMC
December 2019

Chemically stable inhibitors of 14-3-3 protein-protein interactions derived from BV02.

J Enzyme Inhib Med Chem 2019 Dec;34(1):657-664

a Department of Biotechnology, Chemistry and Pharmacy , Università degli Studi di Siena , Siena , Italy.

14-3-3 are regulatory proteins that through protein-protein interactions (PPI) with numerous binding partners could be involved in several human diseases, including cancer, neurodegenerative disorders, and pathogens infections. Following our research interest in the development of 14-3-3 PPI inhibitors, here we exploited the privileged 4-aminoantipyrine scaffold in the design and synthesis of some derivatives endowed with antiproliferative activity against K-562 cells, and capable of binding to recombinant 14-3-3σ as evidenced by NMR spectroscopy. The binding mode was further explored by molecular modelling, while coupling confocal microscopy with intensitometric analysis showed that compound 1 was able to promote the nuclear translocation of c-Abl at low micromolar concentrations. Read More

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https://www.tandfonline.com/doi/full/10.1080/14756366.2019.1
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http://dx.doi.org/10.1080/14756366.2019.1574779DOI Listing
December 2019
2 Reads

Development of a novel, high-affinity ssDNA trypsin inhibitor.

J Enzyme Inhib Med Chem 2019 Dec;34(1):638-643

a Malopolska Centre of Biotechnology , Jagiellonian University , Krakow , Poland.

Inhibitors of serine proteases are not only extremely useful in the basic research but are also applied extensively in clinical settings. Using Systematic Evolution of Ligands by Exponential Enrichment (SELEX) approach we developed a family of novel, single-stranded DNA aptamers capable of specific trypsin inhibition. Our most potent candidate (T24) and its short version (T59) were thoroughly characterised in terms of efficacy. Read More

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http://dx.doi.org/10.1080/14756366.2019.1569648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366424PMC
December 2019

Design and synthesis of 4-piperazinyl quinoline derived urea/thioureas for anti-breast cancer activity by a hybrid pharmacophore approach.

J Enzyme Inhib Med Chem 2019 Dec;34(1):620-630

a Health Sciences North Research Institute , Sudbury , Canada.

In an attempt to improve anti-breast cancer activity, a new series of 4-piperazinylquinoline derivatives based on the urea/thiourea scaffold were designed and synthesised by a pharmacophore hybrid approach. We then examined for their antiproliferative effects on three human breast tumor cell lines, MDA-MB231, MDA-MB468 and MCF7, and two non-cancer breast epithelial cell lines, 184B5 and MCF10A. Among those 26 novel compounds examined, 5, 9, 17, 18, 21, 23 and 29 showed significantly improved antiproliferative activity on breast cancer cells. Read More

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http://dx.doi.org/10.1080/14756366.2019.1571055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366420PMC
December 2019

Inhibition of α-, β-, γ-, δ-, ζ- and η-class carbonic anhydrases from bacteria, fungi, algae, diatoms and protozoans with famotidine.

J Enzyme Inhib Med Chem 2019 Dec;34(1):644-650

a Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche , Università degli Studi di Firenze , Florence , Italy.

Famotidine, an antiulcer drug belonging to the H antagonists class of pharmacological agents, was recently shown to potently inhibit human (h) and bacterial carbonic anhydrases (CAs, EC 4.2.1. Read More

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http://dx.doi.org/10.1080/14756366.2019.1571273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366436PMC
December 2019
1 Read

4-(3-Nitrophenyl)thiazol-2-ylhydrazone derivatives as antioxidants and selective hMAO-B inhibitors: synthesis, biological activity and computational analysis.

J Enzyme Inhib Med Chem 2019 Dec;34(1):597-612

d Dipartimento di Scienze della Salute , "Magna Graecia" University of Catanzaro , Catanzaro , Italy.

A new series of 4-(3-nitrophenyl)thiazol-2-ylhydrazone derivatives were designed, synthesised, and evaluated to assess their inhibitory effect on the human monoamine oxidase (hMAO) A and B isoforms. Different (un)substituted (hetero)aromatic substituents were linked to N1 of the hydrazone in order to establish robust structure-activity relationships. The results of the biological testing demonstrated that the presence of the hydrazothiazole nucleus bearing at C4 a phenyl ring functionalised at the meta position with a nitro group represents an important pharmacophoric feature to obtain selective and reversible human MAO-B inhibition for the treatment of neurodegenerative disorders. Read More

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http://dx.doi.org/10.1080/14756366.2019.1571272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366404PMC
December 2019
2 Reads

Discovery of novel dual-active 3-(4-(dimethylamino)phenyl)-7-aminoalcoxy-coumarin as potent and selective acetylcholinesterase inhibitor and antioxidant.

J Enzyme Inhib Med Chem 2019 Dec;34(1):631-637

a Programa de Pós-Gradução em Química (PPGQ) , Universidade Federal Rural do Rio de Janeiro , Rio de Janeiro , Brazil.

A series of 3-substituted-7-aminoalcoxy-coumarin was designed and evaluated as cholinesterase inhibitors and antioxidants. All compounds were effective in inhibiting AChE with potencies in the nanomolar range. The 3-(4-(dimethylamino)phenyl)-7-aminoethoxy-coumarin (6a) was considered a hit, showing good AChE inhibition potency (IC = 20 nM) and selectivity (IC BuChE/AChE = 354), quite similar to the reference drug donepezil (IC = 6 nM; IC BuChE/AChE = 365), also presenting antioxidant properties, low citotoxicity and good-predicted ADMET properties. Read More

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https://www.tandfonline.com/doi/full/10.1080/14756366.2019.1
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http://dx.doi.org/10.1080/14756366.2019.1571270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366430PMC
December 2019
3 Reads

Effect of cinnamamides on atopic dermatitis through regulation of IL-4 in CD4 cells.

J Enzyme Inhib Med Chem 2019 Dec;34(1):613-619

f College of Pharmacy , Keimyung University , Daegu , Republic of Korea.

This study aimed to evaluate the effects of cinnamamides on atopic dermatitis (AD) and the mechanisms underlying these effects. To this end, the actions of two cinnamamides, (E)-3-(4-hydroxyphenyl)-N-phenylethyl acrylamide (NCT) and N-trans-coumaroyltyramine (NCPA), were determined on AD by orally administering them to mice. Oral administration of the cinnamamides ameliorated the increase in epidermal and dermal thickness as well as mast cell infiltration. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366421PMC
December 2019
1 Read

Evaluation of a flavonoids library for inhibition of pancreatic α-amylase towards a structure-activity relationship.

J Enzyme Inhib Med Chem 2019 Dec;34(1):577-588

a LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy , University of Porto , Porto , Portugal.

α-Amylase has been considered an important therapeutic target for the management of type 2 diabetes mellitus (T2DM), decreasing postprandial hyperglycaemia (PPHG). In the present work, a panel of 40 structurally related flavonoids was tested, concerning their ability to inhibit α-amylase activity, using a microanalysis screening system, an inhibitory kinetic analysis and molecular docking calculations. From the obtained results, it was possible to observe that the flavone with a -Cl ion at 3-position of C-ring, an -OH group at 3'- and 4'- positions of B-ring and at 5- and 7- positions of A-ring and the C2 = C3 double bond, was the most active tested flavonoid, through competitive inhibition. Read More

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https://www.tandfonline.com/doi/full/10.1080/14756366.2018.1
Publisher Site
http://dx.doi.org/10.1080/14756366.2018.1558221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366418PMC
December 2019
4 Reads

Novel 2-indolinones containing a sulfonamide moiety as selective inhibitors of candida β-carbonic anhydrase enzyme.

J Enzyme Inhib Med Chem 2019 Dec;34(1):528-531

b Sezione di Scienza Farmaceutiche, Neurofarba Department , Universita degli Studi di Firenze , Florence , Italy.

Inhibition of the β-carbonic anhydrase (CA, EC 4.2.1. Read More

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http://dx.doi.org/10.1080/14756366.2018.1564045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366411PMC
December 2019

An AGT-based protein-tag system for the labelling and surface immobilization of enzymes on E. coli outer membrane.

J Enzyme Inhib Med Chem 2019 Dec;34(1):490-499

a Department of Biology Agriculture and Food Sciences , Institute of Bioscience and BioResources - National Research Council of Italy , Naples , Italy.

The use of natural systems, such as outer membrane protein A (OmpA), phosphoporin E (PhoE), ice nucleation protein (INP), etc., has been proved very useful for the surface exposure of proteins on the outer membrane of Gram-negative bacteria. These strategies have the clear advantage of unifying in a one-step the production, the purification and the in vivo immobilisation of proteins/biocatalysts onto a specific biological support. Read More

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http://dx.doi.org/10.1080/14756366.2018.1559161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366409PMC
December 2019

Synthesis and in vitro anticancer activity of certain novel 1-(2-methyl-6-arylpyridin-3-yl)-3-phenylureas as apoptosis-inducing agents.

J Enzyme Inhib Med Chem 2019 Dec;34(1):322-332

f Department of Applied Organic Chemistry , National Research Center , Cairo , Egypt.

In connection with our research program on the development of novel anticancer candidates, herein we report the design and synthesis of novel series of 1-(2-methyl-6-arylpyridin-3-yl)-3-phenylureas 5a-l. The target pyridins were evaluated for their in vitro anticancer activity against two cancer cell lines: non-small cell lung cancer A549 cell line and colon cancer HCT-116 cell line. Compound 5l emerged as the most active congener towards both A549 and HCT-116 cell lines with IC values equal to 3. Read More

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http://dx.doi.org/10.1080/14756366.2018.1547286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366416PMC
December 2019
2 Reads

Donepezil + chromone + melatonin hybrids as promising agents for Alzheimer's disease therapy.

J Enzyme Inhib Med Chem 2019 Dec;34(1):479-489

a Neurosciences intégratives et cliniques, Pôle Chimie Organique et Thérapeutique , University Bourgogne Franche-Comté , Besançon , France.

We describe herein the design, multicomponent synthesis and biological studies of new donepezil + chromone + melatonin hybrids as potential agents for Alzheimer's disease (AD) therapy. We have identified compound 14n as promising multitarget small molecule showing strong BuChE inhibition (IC = 11.90 ± 0. Read More

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http://dx.doi.org/10.1080/14756366.2018.1545766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366423PMC
December 2019
1 Read

Virtual design of novel Plasmodium falciparum cysteine protease falcipain-2 hybrid lactone-chalcone and isatin-chalcone inhibitors probing the S2 active site pocket.

J Enzyme Inhib Med Chem 2019 Dec;34(1):547-561

c ICS-UNIDO , Trieste , Italy.

We report computer-aided design of new lactone-chalcone and isatin-chalcone (HLCIC) inhibitors of the falcipain-2 (PfFP-2). 3D models of 15 FP-2:HLCIC1-15 complexes with known observed activity (IC) were prepared to establish a quantitative structure-activity (QSAR) model and linear correlation between relative Gibbs free energy of enzyme:inhibitor complex formation (ΔΔG) and IC: pIC = -0.0236 × ΔΔG+5. Read More

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https://www.tandfonline.com/doi/full/10.1080/14756366.2018.1
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http://dx.doi.org/10.1080/14756366.2018.1564288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352947PMC
December 2019
3 Reads

Computationally driven discovery of phenyl(piperazin-1-yl)methanone derivatives as reversible monoacylglycerol lipase (MAGL) inhibitors.

J Enzyme Inhib Med Chem 2019 Dec;34(1):589-596

a Department of Pharmacy , University of Pisa , Pisa , Italy.

Monoacylglycerol lipase (MAGL) is an attractive therapeutic target for many pathologies, including neurodegenerative diseases, cancer as well as chronic pain and inflammatory pathologies. The identification of reversible MAGL inhibitors, devoid of the side effects associated to prolonged MAGL inactivation, is a hot topic in medicinal chemistry. In this study, a novel phenyl(piperazin-1-yl)methanone inhibitor of MAGL was identified through a virtual screening protocol based on a fingerprint-driven consensus docking (CD) approach. Read More

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http://dx.doi.org/10.1080/14756366.2019.1571271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352951PMC
December 2019
1 Read

Inhibition of protein phosphatase-1 and -2A by ellagitannins: structure-inhibitory potency relationships and influences on cellular systems.

J Enzyme Inhib Med Chem 2019 Dec;34(1):500-509

a Department of Medical Chemistry, Faculty of Medicine , University of Debrecen , Debrecen , Hungary.

Several ellagitannins inhibited the activity of protein phosphatase-1 (PP1) and -2 A (PP2A) catalytic subunits (PP1c and PP2Ac) with preferential suppression of PP1c over PP2Ac. The inhibitory potency for PP1c followed the order of tellimagrandin I > mahtabin A > praecoxin B > 1.2-Di-O-galloyl-4. Read More

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http://dx.doi.org/10.1080/14756366.2018.1557653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352937PMC
December 2019

Phaeodactylum tricornutum as a model organism for testing the membrane penetrability of sulphonamide carbonic anhydrase inhibitors.

J Enzyme Inhib Med Chem 2019 Dec;34(1):510-518

a Institute of Bioscience and BioResources, CNR , Naples , Italy.

Carbonic anhydrases (CAs) are ubiquitous metalloenzymes, which started to be investigated in detail in pathogenic, as well as non-pathogenic species since their pivotal role is to accelerate the physiological CO hydration/dehydration reaction significantly. Here, we propose the marine unicellular diatom Phaeodactylum tricornutum as a model organism for testing the membrane penetrability of CA inhibitors (CAIs). Seven inhibitors belonging to the sulphonamide type and possessing a diverse scaffold have been explored for their in vitro inhibition of the whole diatom CAs and the in vivo inhibitory effect on the growth of P. Read More

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https://www.tandfonline.com/doi/full/10.1080/14756366.2018.1
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http://dx.doi.org/10.1080/14756366.2018.1559840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352938PMC
December 2019
3 Reads

Benzylamides and piperazinoarylamides of ibuprofen as fatty acid amide hydrolase inhibitors.

J Enzyme Inhib Med Chem 2019 Dec;34(1):562-576

a Department of Life and Environmental Sciences - Unit of Pharmaceutical, Pharmacological and Nutraceutical Sciences , University of Cagliari , Cagliari , Italy.

Fatty Acid Amide Hydrolase (FAAH) is a serine hydrolase that plays a key role in controlling endogenous levels of endocannabinoids. FAAH inhibition is considered a powerful approach to enhance the endocannabinoid signalling, and therefore it has been largely studied as a potential target for the treatment of neurological disorders such as anxiety or depression, or of inflammatory processes. We present two novel series of amide derivatives of ibuprofen designed as analogues of our reference FAAH inhibitor Ibu-AM5 to further explore its structure-activity relationships. Read More

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http://dx.doi.org/10.1080/14756366.2018.1532418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352954PMC
December 2019

Chemical composition and enzyme inhibition of Phytolacca dioica L. seeds extracts.

J Enzyme Inhib Med Chem 2019 Dec;34(1):519-527

a Department of Life and Environmental Sciences , University of Cagliari , Monserrato , Italy.

Phytolacca, which belongs to the family of Phytolaccaceae, are known for their use in popular medicine. Bioactivity of five extracts from Phytolacca dioica seeds were evaluated in four bioassays. A selected group of compounds from the extract that displayed the best bioactivity was analysed. Read More

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https://www.tandfonline.com/doi/full/10.1080/14756366.2018.1
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http://dx.doi.org/10.1080/14756366.2018.1563077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352939PMC
December 2019
4 Reads
2.383 Impact Factor

Novel pyrazolo[3,4-d]pyrimidines: design, synthesis, anticancer activity, dual EGFR/ErbB2 receptor tyrosine kinases inhibitory activity, effects on cell cycle profile and caspase-3-mediated apoptosis.

J Enzyme Inhib Med Chem 2019 Dec;34(1):532-546

a Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy , Cairo University , Cairo , Egypt.

A series of novel pyrazolo[3,4-d]pyrimidines was synthesised. Twelve synthesised compounds were evaluated for their anticancer activity against 60 human tumour cell lines by NCI (USA). Compound 7d proved prominent anticancer activity. Read More

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https://www.tandfonline.com/doi/full/10.1080/14756366.2018.1
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http://dx.doi.org/10.1080/14756366.2018.1564046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352943PMC
December 2019
3 Reads

Comparison of blood carbonic anhydrase activity of athletes performing interval and continuous running exercise at high altitude.

J Enzyme Inhib Med Chem 2019 Dec;34(1):218-224

f Section of Pharmaceutical Chemistry, Neurofarba Department , University of Florence , Firenze, Italy.

The effects of high-intensity interval and continuous exercise on erythrocytes carbonic anhydrase (CA, EC 4.2.1. Read More

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http://dx.doi.org/10.1080/14756366.2018.1545768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292344PMC
December 2019

Synthesis and biological assessment of KojoTacrines as new agents for Alzheimer's disease therapy.

J Enzyme Inhib Med Chem 2019 Dec;34(1):163-170

b Laboratoire de Chimie Organique et Thérapeutique, Neurosciences Intégratives et Cliniques EA 481 , Univ. Bourgogne Franche-Comté , Besançon , France.

In view of the multifactorial nature of Alzheimer's disease (AD), multitarget small molecules (MTSM) represent the most potent and attractive therapeutic strategy to design new drugs for Alzheimer's disease therapy. The new MTSM KojoTacrines (KTs) were designed and synthesized by juxtaposition of selected pharmacophoric motifs from kojic acid and tacrine. Among them, 11-amino-2-(hydroxymethyl)-12-(3-methoxyphenyl)-7,9,10,12-tetrahydropyrano [2',3':5,6] pyrano[2,3-b]quinolin-4(8H)-one (KT2d) was identified as less-hepatotoxic than tacrine, at higher concentration, a moderate, but selective human acetylcholinesterase inhibitor (IC = 4. Read More

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http://dx.doi.org/10.1080/14756366.2018.1538136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263107PMC
December 2019

Synthesis and biological evaluation of benzothiazin-4-ones: a possible new class of acetylcholinesterase inhibitors.

J Enzyme Inhib Med Chem 2019 Dec;34(1):197-203

a Laboratório de Química Aplicada a Bioativos, Centro Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas , Prédio 32, Laboratório 410, Campus Universitário S/N , Capão do Leão , RS , CEP 96160-000 , Brazil.

A series of nineteen benzothiazin-4-ones from N-(3-aminopropyl) piperidine, 4-(2-aminoethyl)morpholine or 1-(2-aminoethyl)piperidine, aliphatic or aromatic aldehyde and thiosalicylic acid, were synthesized in good yields by multicomponent one-pot reactions. The solvent was toluene and this efficient procedure afforded the desired heterocycles in 5 h. Identification and characterization were achieved by NMR and GC-MS techniques. Read More

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http://dx.doi.org/10.1080/14756366.2018.1543286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263113PMC
December 2019
1 Read

Carbonic anhydrase 12 mutation modulates membrane stability and volume regulation of aquaporin 5.

J Enzyme Inhib Med Chem 2019 Dec;34(1):179-188

a Department of Physiology , College of Medicine, Gachon University , Incheon , Republic of Korea.

Patients carrying the carbonic anhydrase12 E143K mutation showed the dry mouth phenotype. The mechanism underlying the modulation of aquaporin 5 and function in the salivary glands by carbonic anhydrase12 remains unknown. In this study, we identified the mislocalised aquaporin 5 in the salivary glands carrying the E143K. Read More

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http://dx.doi.org/10.1080/14756366.2018.1540475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249555PMC
December 2019
10 Reads

Repurposing existing drugs: identification of irreversible IMPDH inhibitors by high-throughput screening.

J Enzyme Inhib Med Chem 2019 Dec;34(1):171-178

a Division of Applied Bioscience, Graduate School of Agriculture , Hokkaido University , Sapporo , Japan.

Inosine 5'-monophosphate dehydrogenase (IMPDH) is an essential enzyme for the production of guanine nucleotides. Disruption of IMPDH activity has been explored as a therapeutic strategy for numerous purposes, such as for anticancer, immunosuppression, antiviral, and antimicrobial therapy. In the present study, we established a luciferase-based high-throughput screening system to identify IMPDH inhibitors from our chemical library of known bioactive small molecules. Read More

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https://www.tandfonline.com/doi/full/10.1080/14756366.2018.1
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http://dx.doi.org/10.1080/14756366.2018.1540474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249553PMC
December 2019
21 Reads

HPLC-UV assay for the evaluation of inhibitors of plasma amine oxidase using crude bovine plasma.

J Enzyme Inhib Med Chem 2019 Dec;34(1):144-149

a Institute of Pharmaceutical and Medicinal Chemistry, University of Münster , Münster , Germany.

Recently, we have described a method for evaluation of plasma amine oxidase (PAO) inhibitors, which monitors the formation of 6-(5-phenyl-2H-tetrazol-2-yl)hexanal from the corresponding amine substrate by HPLC with UV-detection using purified bovine PAO. We now investigated, whether crude bovine plasma can be used as enzyme source in this assay instead of the purified enzyme. With the aid of specific inhibitors, it was ensured that there was no detectable activity of other important amine oxidases in the plasma, namely monoamine oxidase (MAO) A and B and diamine oxidase (DAO). Read More

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https://www.tandfonline.com/doi/full/10.1080/14756366.2018.1
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http://dx.doi.org/10.1080/14756366.2018.1524890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237158PMC
December 2019
5 Reads