2,285 results match your criteria Journal of Enzyme Inhibition and Medicinal Chemistry [Journal]


Design, synthesis and molecular mechanisms of novel dual inhibitors of heat shock protein 90/phosphoinositide 3-kinase alpha (Hsp90/PI3Kα) against cutaneous melanoma.

J Enzyme Inhib Med Chem 2019 Dec;34(1):909-926

a Department of Dermatology, State Key Laboratory of Biotherapy , West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy , Chengdu , China.

Overexpression of heat shock protein 90 (Hsp90) is common in various types of cancer. In cutaneous melanoma, a cancer with one of the high levels of Hsp90 overexpression, such expression was correlated with a panel of protein kinases, thus offering an opportunity to identify Hsp90-based multi-kinase inhibitors for novel cancer therapies. Towards this goal, we utilized a 2,4-dihydroxy-5-isopropylbenzate-based Hsp90 inhibitor scaffold and thieno[2,3-d]pyrimidine-based kinase inhibitor scaffold to develop a Hsp90-inhibiting compound library. Read More

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http://dx.doi.org/10.1080/14756366.2019.1596903DOI Listing
December 2019

Antioxidant activity and antibacterial evaluation of new thiazolin-4-one derivatives as potential tryptophanyl-tRNA synthetase inhibitors.

J Enzyme Inhib Med Chem 2019 Dec;34(1):898-908

a Department of Pharmaceutical Chemistry , "Iuliu Haţieganu" University of Medicine and Pharmacy , Cluj-Napoca , Romania.

The rapid emergence of bacterial resistance to antibiotics currently available for treating infectious diseases requires effective antimicrobial agents with new structural profiles and mechanisms of action. Twenty-three thiazolin-4-one derivatives were evaluated for their antibacterial activity by determining the growth inhibition zone diameter, the minimum inhibitory concentration (MIC), and the minimum bactericidal concentration (MBC), against gram-positive and gram-negative bacteria. Compounds 3a-c, 3e-h, 6b-c and 9a-c expressed better MIC values than moxifloxacin, against Staphylococcus aureus. Read More

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http://dx.doi.org/10.1080/14756366.2019.1596086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450493PMC
December 2019
4 Reads

In vitro investigating of anticancer activity of new 7-MEOTA-tacrine heterodimers.

J Enzyme Inhib Med Chem 2019 Dec;34(1):877-897

a Department of Biochemistry, Institute of Chemistry, Faculty of Science , P. J. Šafárik University , Kosice , Slovak Republic.

A combination of biochemical, biophysical and biological techniques was used to study calf thymus DNA interaction with newly synthesized 7-MEOTA-tacrine thiourea 12-17 and urea heterodimers 18-22, and to measure interference with type I and II topoisomerases. Their biological profile was also inspected in vitro on the HL-60 cell line using different flow cytometric techniques (cell cycle distribution, detection of mitochondrial membrane potential dissipation, and analysis of metabolic activity/viability). The compounds exhibited a profound inhibitory effect on topoisomerase activity (e. 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/10.1080/14756366.2019.1593159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450562PMC
December 2019
2 Reads

Novel thienopyrimidine derivatives as dual EGFR and VEGFR-2 inhibitors: design, synthesis, anticancer activity and effect on cell cycle profile.

J Enzyme Inhib Med Chem 2019 Dec;34(1):838-852

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

Aim: Design and synthesis of thienopyrimidine derivatives as dual EGFR and VEGFR-2 inhibitors.

Material And Methods: A series of novel 6,7,8,9-tetrahydro-5H-cyclohepta[4,5]thieno[2,3-d]pyrimidine derivatives with different substituents on C-4 position was synthesized and evaluated for their anticancer activity against MCF-7 cell line. EGFR, VEGFR-2 inhibitory assay, the cell cycle analysis and apoptosis induction ability of the most potent compound 5f were evaluated. Read More

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http://dx.doi.org/10.1080/14756366.2019.1593160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442109PMC
December 2019

Design, synthesis, and apoptosis-promoting effect evaluation of novel pyrazole with benzo[d]thiazole derivatives containing aminoguanidine units.

J Enzyme Inhib Med Chem 2019 Dec;34(1):829-837

a School of Pharmacy, Bengbu Medical College , Bengbu , China.

New pyrazole with benzo[d]thiazoles containing hydrazinecarboximidamide substituent was synthesised and evaluated for cytotoxicity and apoptotic activity using the MTT assay, flow cytometry, and Western blot analysis. Among the compounds studied, (E)-2-((1-(6-((4-fluorobenzyl)oxy)benzo[d]thiazol-2-yl)-3-phenyl-1H- pyrazol-4-yl)methylene) hydrazinecarboximidamide (8l) was potent, with IC values of 2.41 µM, 2. 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/10.1080/14756366.2019.1591391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442160PMC
December 2019
3 Reads

SAR and molecular mechanism studies of monoamine oxidase inhibition by selected chalcone analogs.

J Enzyme Inhib Med Chem 2019 Dec;34(1):863-876

a Department of Pharmaceutical Sciences, College of Pharmacy , Qatar University , Doha , Qatar.

The present study describes the synthesis of a series of 22 chalcone analogs. These compounds were evaluated as potential human MAO-A and MAO-B inhibitors. The compounds showed varied selectivity against the two isoforms. Read More

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http://dx.doi.org/10.1080/14756366.2019.1593158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442233PMC
December 2019

The antitumor activity of CYB-L10, a human topoisomerase IB catalytic inhibitor.

J Enzyme Inhib Med Chem 2019 Dec;34(1):818-822

a School of Pharmaceutical Sciences , Sun Yat-sen University , Guangzhou , China.

DNA topoisomerase IB (TOP1) is a validated target for discovery and development of antitumor agents. Four TOP1 poisons are clinically used for tumor treatment now. In spite of their effectiveness in solid tumors, these camptothecin (CPT) poisons suffer from many shortcomings. Read More

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http://dx.doi.org/10.1080/14756366.2018.1516651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442119PMC
December 2019

New insight into structure-activity of furan-based salicylate synthase (MbtI) inhibitors as potential antitubercular agents.

J Enzyme Inhib Med Chem 2019 Dec;34(1):823-828

b Department of Pharmaceutical Sciences , University of Milano , Milano , Italy.

Starting from the analysis of the hypothetical binding mode of our previous furan-based hit (I), we successfully achieved our objective to replace the nitro moiety, leading to the disclosure of a new lead exhibiting a strong activity against MbtI. Our best candidate 1 h displayed a K of 8.8 µM and its antimycobacterial activity (MIC = 250 µM) is conceivably related to mycobactin biosynthesis inhibition. 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/10.1080/14756366.2019.1589462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427685PMC
December 2019
4 Reads

Discovery of novel coumarin derivatives as potent and orally bioavailable BRD4 inhibitors based on scaffold hopping.

J Enzyme Inhib Med Chem 2019 Dec;34(1):808-817

a Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province , Institute of Materia Medica, Zhejiang Academy of Medical Sciences , Hangzhou , PR China.

The bromodomain and extra-terminal (BET) bromodomains, particularly BRD4, have been identified as promising therapeutic targets in the treatment of many human disorders such as cancer, inflammation, obesity, and cardiovascular disease. Recently, the discovery of novel BRD4 inhibitors has garnered substantial interest. Starting from scaffold hopping of the reported compound dihydroquinazolinone (PFI-1), a series of coumarin derivatives were designed and synthesised as a new chemotype of BRD4 inhibitors. 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/10.1080/14756366.2019.1587417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427567PMC
December 2019
6 Reads

CRISPR/Cas9-based liver-derived reporter cells for screening of mPGES-1 inhibitors.

J Enzyme Inhib Med Chem 2019 Dec;34(1):799-807

a Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital , Fuzhou , China.

mPGES-1 is a terminal rate-limiting enzyme responsible for inflammation-induced PGE2 production. The inhibition of mPGES-1 has been considered as a safe and effective target for the treatment of inflammation and cancer. However, a specific, efficient, and simple method for high-throughput screening of mPGES-1 inhibitors is still lacking. Read More

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http://dx.doi.org/10.1080/14756366.2019.1587416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427568PMC
December 2019
1 Read

The protective role of jervine against radiation-induced gastrointestinal toxicity.

J Enzyme Inhib Med Chem 2019 Dec;34(1):789-798

i Department of Chemistry, Faculty of Science and Literature , Kilis 7 Aralık University , Kilis , Turkey.

In this study, we investigated whether jervine (J) could prevent gastrointestinal (GI) side effects of abdominopelvic radiotherapy (RT) in Wistar-Albino female rats. Rats were divided into five groups: control (C), J only (J), J administered at 5 mg/kg/days for 7 days, RT only (RT), J before RT (J + RT), J administered for seven days before RT, J both before and after RT (J + RT + J), and J administered for 7 days before RT and after RT for 3 days. The weights of rats were measured on the 1st, 7th, and 10th days of the study. Read More

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http://dx.doi.org/10.1080/14756366.2019.1586681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419660PMC
December 2019

Osteopontin - a biomarker of disease, but also of stage stratification of the functional myocardial contractile deficit by chronic ischaemic heart disease.

J Enzyme Inhib Med Chem 2019 Dec;34(1):783-788

g Faculty of Sciences , University of Pitesti , Pitesti , Romania.

The study analyses the significance of the plasmatic values of the OPN dosed to 91 people suffering from diastolic cardiac dysfunction with preserved ejection fraction, thus revealing significant growths of its level compared to the normal value. Despite being a clinical research, its conclusions are a breakthrough, differing from the results of other studies published in the relevant medical literature. We can make this assertion because this study analyses the clinical information given by the circulating values of the OPN, based on experimental models (animals), or on patients with congestive heart failure, which can be identified with the existence of a low systolic flow. Read More

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http://dx.doi.org/10.1080/14756366.2019.1587418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407584PMC
December 2019
2.383 Impact Factor

Novel Re(I) tricarbonyl coordination compounds based on 2-pyridyl-1,2,3-triazole derivatives bearing a 4-amino-substituted benzenesulfonamide arm: synthesis, crystal structure, computational studies and inhibitory activity against carbonic anhydrase I, II, and IX isoforms†.

J Enzyme Inhib Med Chem 2019 Dec;34(1):773-782

a Laboratoire de Chimie, physique Université du 8 Mai 1945 , Guelma , Algérie.

In this work, two bidentate 2-pyridyl-1,2,3-triazole ligands (3a and 3b) containing a 4-substituted benzenesulfonamide pharmacophore prepared by classical click chemistry procedures, as well as their corresponding rhenium complexes, 4a and 4b of general formula [ReCl(CO)(L)] (L = 3a or 3b) were prepared and fully characterised by spectroscopic methods (IR, NMR, MS, UV-Vis), elemental analysis, X-ray diffraction, and theoretical studies using DFT and TD-DFT methods. In particular, we showed that, in the solid state, the pyridine and the triazole rings of 3b adopted an uncommon cis configuration which stems from intermolecular hydrogen bonds. Preliminary assays demonstrated a promising nanomolar inhibitory activity against carbonic anhydrase isoform IX for both ligands and complexes with a strong affinity K of 2. Read More

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http://dx.doi.org/10.1080/14756366.2019.1585835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407592PMC
December 2019

Synthesis and biological evaluation of ursolic acid derivatives bearing triazole moieties as potential anti-Toxoplasma gondii agents.

J Enzyme Inhib Med Chem 2019 Dec;34(1):761-772

a Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy , Yanbian University , Yanji , Jilin , China.

Ursolic acid (UA), a plant-derived compound, has many properties beneficial to health. In the present study, we synthesised three series of novel UA derivatives and evaluated their anti-Toxoplasma gondii activity both in vitro and in vivo. Most derivatives exhibited an improved anti-T. Read More

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http://dx.doi.org/10.1080/14756366.2019.1584622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407578PMC
December 2019
2 Reads

Design, synthesis and biological evaluation of novel 4-anlinoquinazoline derivatives as EGFR inhibitors with the potential to inhibit the gefitinib-resistant nonsmall cell lung cancers.

J Enzyme Inhib Med Chem 2019 Dec;34(1):203-217

a Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy , Jiangxi Science & Technology Normal University , Nanchang , Jiangxi , China.

A series of quinazoline derivatives with benzylidene hydrazine carboxamide were designed and synthesised as EGFR inhibitors. Most compounds exhibited exceptional anti-proliferative activity against A549, HepG2, MCF-7 and H1975 cells. Furthermore, six compounds demonstrated excellent inhibition activity against EGFR with the IC value both less than 2 nM. Read More

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http://dx.doi.org/10.1080/14756366.2018.1518957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282443PMC
December 2019

Inhibition potential of phenolic constituents from the aerial parts of Tetrastigma hemsleyanum against soluble epoxide hydrolase and nitric oxide synthase.

J Enzyme Inhib Med Chem 2019 Dec;34(1):753-760

a College of Pharmacy, Chungnam National University , Daejeon , Korea.

The aerial parts of Tetrastigma hemsleyanum (APTH) have been used as a functional tea in China. The purpose of the current study was to identify the bioactive constituents with inhibitory activity against soluble epoxide hydrolase (sEH) and inducible nitric oxide synthase (iNOS), which are jointly considered potential therapeutic targets for vascular system diseases. In the present study, 39 compounds (1-39) were isolated from the APTH. Read More

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http://dx.doi.org/10.1080/14756366.2019.1584621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407587PMC
December 2019
1 Read

Exploring the activity of polyamine analogues on polyamine and spermine oxidase: methoctramine, a potent and selective inhibitor of polyamine oxidase.

J Enzyme Inhib Med Chem 2019 Dec;34(1):740-752

d Department of Pharmacy and Biotechnology , Alma Mater Studiorum-University of Bologna , Bologna , Italy.

Fourteen polyamine analogues, asymmetric or symmetric substituted spermine (1-9) or methoctramine (10-14) analogues, were evaluated as potential inhibitors or substrates of two enzymes of the polyamine catabolic pathway, spermine oxidase (SMOX) and acetylpolyamine oxidase (PAOX). Compound 2 turned out to be the best substrate for PAOX, having the highest affinity and catalytic efficiency with respect to its physiological substrates. Methoctramine (10), a well-known muscarinic M receptor antagonist, emerged as the most potent competitive PAOX inhibitor known so far (K = 10 nM), endowed with very good selectivity compared with SMOX (K=1. Read More

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http://dx.doi.org/10.1080/14756366.2019.1584620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407594PMC
December 2019
1 Read

Delivering bioactive cyclic peptides that target Hsp90 as prodrugs.

J Enzyme Inhib Med Chem 2019 Dec;34(1):728-739

a School of Chemistry, University of New South Wales , Sydney , Australia.

The most challenging issue facing peptide drug development is producing a molecule with optimal physical properties while maintaining target binding affinity. Masking peptides with protecting groups that can be removed inside the cell, produces a cell-permeable peptide, which theoretically can maintain its biological activity. Described are series of prodrugs masked using: (a) O-alkyl, (b) N-alkyl, and (c) acetyl groups, and their binding affinity for Hsp90. Read More

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http://dx.doi.org/10.1080/14756366.2019.1580276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407599PMC
December 2019
5 Reads
2.383 Impact Factor

Synthesis and evaluation of anticancer, antiphospholipases, antiproteases, and antimetabolic syndrome activities of some 3H-quinazolin-4-one derivatives.

J Enzyme Inhib Med Chem 2019 Dec;34(1):672-683

e Department of Chemistry , Kulliyyah of Science, International Islamic University Malaysia , Kuantan , Pahang Darul Makmur,   Malaysia.

Some new 3H-quinazolin-4-one derivatives were synthesised and screened for anticancer, antiphospholipases, antiproteases, and antimetabolic syndrome activities. Compound 15d was more potent in reducing the cell viabilities of HT-29 and SW620 cells lines to 38%, 36.7%, compared to 5-FU which demonstrated cell viabilities of 65. Read More

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http://dx.doi.org/10.1080/14756366.2019.1574780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407576PMC
December 2019
3 Reads

Evaluation of the anticancer potential of a sulphonamide carbonic anhydrase IX inhibitor on cervical cancer cells.

J Enzyme Inhib Med Chem 2019 Dec;34(1):703-711

d Neurofarba Department, Section of Pharmaceutical and Nutriceutical Sciences , Università degli Studi di Firenze , Sesto Fiorentino (Florence) , Italy.

Cervical cancer is a common type of cancer. Carbonic anhydrase IX (CA IX) is an attractive target for tumour therapy, being overexpressed in many cancers. We investigated the anticancer properties of the aromatic sulphonamide S-1 as a CA IX inhibitor on cervical cancer cells (HeLa) positive for CA IX expression and normal prostate epithelial cell line (PNT1-A) negative for CA IX. Read More

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http://dx.doi.org/10.1080/14756366.2019.1579805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394301PMC
December 2019
2 Reads

In vitro modulation of multidrug resistance by pregnane steroids and in vivo inhibition of tumour development by 7α-OBz-11α(R)-OTHP-5β-pregnanedione in K562/R7 and H295R cell xenografts.

J Enzyme Inhib Med Chem 2019 Dec;34(1):684-691

a ISPB-Faculté de Pharmacie , Université de Lyon, Université Lyon 1 , Lyon , France.

Synthetic progesterone and 5α/β-pregnane-3,20-dione derivatives were evaluated as in vitro and in vivo modulators of multidrug-resistance (MDR) using two P-gp-expressing human cell lines, the non-steroidogenic K562/R7 erythroleukaemia cells and the steroidogenic NCI-H295R adrenocortical carcinoma cells, both resistant to doxorubicin. The maximal effect in both cell lines was observed for 7α-O-benzoyloxy,11α(R)-O-tetrahydropyranyloxy-5β-pregnane-3,20-dione 4. This modulator co-injected with doxorubicin significantly decreased the tumour size and increased the survival time of immunodeficient mice xenografted with NCI-H295R or K562/R7 cells. Read More

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http://dx.doi.org/10.1080/14756366.2019.1575825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383615PMC
December 2019
3 Reads

Aberrant regulation favours matriptase proteolysis in neoplastic B-cells that co-express HAI-2.

J Enzyme Inhib Med Chem 2019 Dec;34(1):692-702

a Lombardi Comprehensive Cancer Center, Department of Oncology , Georgetown University , Washington , DC, USA.

Matriptase is ectopically expressed in neoplastic B-cells, in which matriptase activity is enhanced by negligible expression of its endogenous inhibitor, hepatocyte growth factor activator inhibitor (HAI)-1. HAI-1, however, is also involved in matriptase synthesis and intracellular trafficking. The lack of HAI-1 indicates that other related inhibitor, such as HAI-2, might be expressed. Read More

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http://dx.doi.org/10.1080/14756366.2019.1577831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383611PMC
December 2019
5 Reads
2.383 Impact Factor

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374920PMC
December 2019
1 Read

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374954PMC
December 2019
4 Reads

(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
3 Reads

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
1 Read

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
1 Read

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
8 Reads

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
3 Reads

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
1 Read

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
2 Reads

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
3 Reads
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
2 Reads

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
2 Reads

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
8 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
1 Read

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
1 Read

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
4 Reads

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
Publisher Site
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
1 Read

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
2 Reads