9,520 results match your criteria European Journal of Medicinal Chemistry [Journal]


Synthesis of novel andrographolide beckmann rearrangement derivatives and evaluation of their HK2-related anti-inflammatory activities.

Eur J Med Chem 2019 Apr 16;173:282-293. Epub 2019 Apr 16.

Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address:

Two series of andrographolide derivatives with introduction of amide moiety into ring A by Beckmann rearrangement were synthesized. In series 1, the ring A was converted to caprolactam, and an amide moiety was linked to C-19 of ring A in series 2. Among them, compound 8h exhibited obvious inhibition on HK2 enzyme activity (IC = 9. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.04.022DOI Listing
April 2019
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Antibacterial activity study of 1,2,4-triazole derivatives.

Eur J Med Chem 2019 Apr 16;173:274-281. Epub 2019 Apr 16.

Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, PR China. Electronic address:

Antibiotics are commonly used to fight against bacterial infections, but bacteria have already been resistant to almost all antibiotics due to abuse of antibiotics. 1,2,4-Triazole derived compounds possess chemotherapeutic effects including potential antibacterial activities against drug-sensitive as well as drug-resistant pathogens. Hybridization displays a high potential to develop novel drugs with the capacity to overcome drug resistance, reduce toxicity and improve pharmacokinetic profiles. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.04.043DOI Listing

Multitarget PPARγ agonists as innovative modulators of the metabolic syndrome.

Eur J Med Chem 2019 Apr 13;173:261-273. Epub 2019 Apr 13.

Department of Pharmacy, University of Chieti "G. d.Annunzio", Via Dei Vestini, 31, 66100, Chieti, Italy.

A multitarget pharmacologic approach could be advantageous for the therapy of metabolic multiple diseases, such as the metabolic syndrome, which is characterized by metabolic abnormalities associated with diabetes, obesity, hypertension, and increased cardiovascular risk. PPAR receptors play a critical role in metabolic disorders, affecting glucose and lipid metabolism. Drugs simultaneously targeting PPAR and other validated metabolic targets, represent a promising multitarget approach to combine antihyperglycemic, antihyperlipidemic, and antihypertensive effects. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.04.030DOI Listing

Synthesis and immunological studies of β-1,2-mannan-peptide conjugates as antifungal vaccines.

Eur J Med Chem 2019 Apr 5;173:250-260. Epub 2019 Apr 5.

Department of Chemistry, University of Florida, 214 Leigh Hall, Gainesville, FL, 32611, USA. Electronic address:

Fungal cell surface carbohydrates and proteins are useful antigens for the development of antifungal vaccines. In this study, glycopeptides consisting of the β-1,2-mannan and N-terminal peptide epitopes of Candida albicans (C. albicans) cell wall phosphomannan complex and Als1p (rAls1p-N) protein, respectively, were synthesized and covalently conjugated with keyhole limpet hemocyanin (KLH) and human serum albumin (HSA) through homobifunctional disuccinimidyl glutarate. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.04.001DOI Listing

Design, synthesis and docking studies of benzimidazole derivatives as potential EGFR inhibitors.

Eur J Med Chem 2019 Apr 9;173:240-249. Epub 2019 Apr 9.

Ankara University, Faculty of Pharmacy, Department of Pharmacology, 06100, Tandoğan-Ankara, Turkey.

In this study, a series of benzimidazoles bearing thiosemicarbazide chain or triazole and thiadiazole rings were designed and synthesized. Crystal and molecular structure of the compound 5c has been characterized by single crystal X-ray crystallographic analysis. EGFR kinase inhibitory potencies of synthesized compounds were compared with erlotinib in vitro and most of the compounds exhibited significant activities. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.04.012DOI Listing

Design, synthesis and biological evaluation of novel neuchromenin analogues as potential antifungal agents.

Eur J Med Chem 2019 Apr 14;173:228-239. Epub 2019 Apr 14.

Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry and Pharmacy, Northwest A&F University, Yangling, 712100, Shaanxi Province, China. Electronic address:

In continuation of our program to discover new potential antifungal agents, thirty-two neuchromenin analogues were synthesized and characterized by the spectroscopic analysis. By using the mycelium growth rate method, the target compounds were evaluated systematically for antifungal activities in vitro against six plant pathogenic fungi, and structure-activity relationships (SAR) were derived. Compounds 6b-c, and 6l showed obvious inhibition activity on each of the fungi at 50 μg/mL. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.04.029DOI Listing

Research progress in the biological activities of 3,4,5-trimethoxycinnamic acid (TMCA) derivatives.

Eur J Med Chem 2019 Apr 6;173:213-227. Epub 2019 Apr 6.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, 229 Taibai Road, Xi'an, 710069, China. Electronic address:

TMCA (3,4,5-trimethoxycinnamic acid) ester and amide are privileged structural scaffolds in drug discovery which are widely distributed in natural products and consequently produced diverse therapeutically relevant pharmacological functions. Owing to the potential of TMCA ester and amide analogues as therapeutic agents, researches on chemical syntheses and modifications have been carried out to drug-like candidates with broad range of medicinal properties such as antitumor, antiviral, CNS (central nervous system) agents, antimicrobial, anti-inflammatory and hematologic agents for a long time. At the same time, SAR (structure-activity relationship) studies have draw greater attention among medicinal chemists, and many of the lead compounds were derived for various disease targets. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.04.009DOI Listing

Discovery of coumarin Mannich base derivatives as multifunctional agents against monoamine oxidase B and neuroinflammation for the treatment of Parkinson's disease.

Eur J Med Chem 2019 Apr 12;173:203-212. Epub 2019 Apr 12.

Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China. Electronic address:

Due to the complexity of the pathogenesis of Parkinson's disease (PD), multimodal treatment may achieve better results. In this study, a series of coumarin Mannich base derivatives were designed and synthesized as multifunctional agents for PD treatment. Among the derivatives, 3-(3-(dimethylamino)propanoyl)-7-hydroxy-5-methyl- 2H-chromen-2-one hydrochloride (24) exhibited the most potent and selective hMAO-B inhibitory activity, and anti-inflammatory and neuroprotective effects in the in vitro studies. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.04.016DOI Listing

Design, synthesis and biological evaluation of novel thioquinazolinone-based 2-aminobenzamide derivatives as potent histone deacetylase (HDAC) inhibitors.

Eur J Med Chem 2019 Apr 11;173:185-202. Epub 2019 Apr 11.

Key Laboratory of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology), Ministry of Education. College of Life Science and Technology, Beijing University of Chemical Technology, 15 Beisanhuan East Road, Beijing, 100029, China. Electronic address:

A series of novel 2-aminobenzamide derivatives decorated with thioquinazolinone were designed and synthesized as histone deacetylase (HDAC) inhibitors. These derivatives were evaluated for their antiproliferative activities against several human cancer cell lines including A375, Hela, A549, HCT116 and SMMC7721. It's significantly indicated that some inhibitors exhibited potent antiproliferative activities towards all the studied cancer cell lines. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.04.017DOI Listing
April 2019
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Corrigendum to <'Synthesis and biological evaluation of 2,6-disubstituted-9H-purine, 2,4-disubstitued-thieno[3,2-d]pyrimidine and -7H-pyrrolo[2,3-d] pyrimidine analogues as novel CHK1 inhibitors' [Eur. J. Med. Chem. 151 (2018) 836-848].

Eur J Med Chem 2019 Apr 16;173:184. Epub 2019 Apr 16.

Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China. Electronic address:

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http://dx.doi.org/10.1016/j.ejmech.2019.04.011DOI Listing
April 2019
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Discovery of 7H-pyrrolo[2,3-d]pyrimidine derivatives as selective covalent irreversible inhibitors of interleukin-2-inducible T-cell kinase (Itk).

Eur J Med Chem 2019 Mar 26;173:167-183. Epub 2019 Mar 26.

State Key Laboratory of Chemical Oncogenomics, Engineering Laboratory for Chiral Drug Synthesis, School of Chemical Biology and Biotechnology, Shenzhen Graduate School, Peking University, Shenzhen, 518055, China. Electronic address:

Interleukin-2-inducible T-cell kinase (Itk) plays an important role in multiple signal transduction pathways in T and mast cells, and is a potential drug target for treating inflammatory diseases, autoimmune diseases, and T cell leukemia/lymphoma. Herein, we describe the discovery of a series of covalent Itk inhibitors based on the 7H-pyrrolo[2,3-d]pyrimidine scaffold. Placing an appropriate substitution group at a hydration site of the ATP binding pocket of Itk and using a saturated heterocyclic ring as a linker to the reactive group were crucial for selectivity. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.055DOI Listing

Comparative analysis of pyrimidine substituted aminoacyl-sulfamoyl nucleosides as potential inhibitors targeting class I aminoacyl-tRNA synthetases.

Eur J Med Chem 2019 Apr 5;173:154-166. Epub 2019 Apr 5.

Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Herestraat 49 Box 1041, B-3000, Leuven, Belgium. Electronic address:

Aminoacyl-tRNA synthetases (aaRSs) catalyse the ATP-dependent coupling of an amino acid to its cognate tRNA. Being vital for protein translation aaRSs are considered a promising target for the development of novel antimicrobial agents. 5'-O-(N-aminoacyl)-sulfamoyl adenosine (aaSA) is a non-hydrolysable analogue of the aaRS reaction intermediate that has been shown to be a potent inhibitor of this enzyme family but is prone to chemical instability and enzymatic modification. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.04.003DOI Listing
April 2019
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Synthetic approaches and pharmaceutical applications of chloro-containing molecules for drug discovery: A critical review.

Eur J Med Chem 2019 Apr 10;173:117-153. Epub 2019 Apr 10.

School of Chemistry, Chemical Engineering and Life Science, School of Materials Science and Engineering, Wuhan University of Technology, 205 Luoshi Road, Wuhan, 430070, PR China. Electronic address:

At present more than 250 FDA approved chlorine containing drugs were available in the market and many pharmaceutically important drug candidates in pre-clinical trials. Thus, it is quite obvious to expect that in coming decades there will be an even greater number of new chlorine-containing pharmaceuticals in market. Chlorinated compounds represent the family of compounds promising for use in medicinal chemistry. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.063DOI Listing
April 2019
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Synthesis and biological evaluation of pyrazolo[3,4-b]pyridine-3-yl pyrimidine derivatives as sGC stimulators for the treatment of pulmonary hypertension.

Eur J Med Chem 2019 Apr 10;173:107-116. Epub 2019 Apr 10.

State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR China; Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR China.

A series of new pyrazolo[3,4-b]pyridin-3-yl pyrimidine derivatives were synthesized and evaluated for the activation of sGC. Compared with riociguat, compound 13a exhibited equivalent in vitro activity on preconstricted rat thoracic aorta rings and in Rat heart Langendorff preparation. Compound 13a also showed acceptable PK profiles, which might become a promising candidate for the treatment of pulmonary hypertension. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.04.014DOI Listing

An oligonucleotide probe incorporating the chromophore of green fluorescent protein is useful for the detection of HER-2 mRNA breast cancer marker.

Eur J Med Chem 2019 Apr 9;173:99-106. Epub 2019 Apr 9.

Department of Chemistry, Bar-Ilan University, Ramat-Gan, 52900, Israel. Electronic address:

Diagnosis and treatment of breast cancer can be greatly enhanced and personalized based on the quantitative detection of mRNA markers. Here, we targeted the development of a fluorescent oligonucleotide probe to detect specifically the HER-2 mRNA breast cancer marker. We have selected the chromophore of the Green Fluorescent Protein (GFP), 4-hydroxybenzylidene imidazolinone (HBI), as a fluorophore covalently bound to an oligonucleotide probe and potentially capable of intercalating within a probe-mRNA duplex. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.04.013DOI Listing
April 2019
2 Reads

Anti-trypanosomal activity of doubly modified salinomycin derivatives.

Eur J Med Chem 2019 Apr 3;173:90-98. Epub 2019 Apr 3.

Department of Bioorganic Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61‒614, Poznań, Poland.

As a group of biologically active compounds, polyether antibiotics (ionophores) show a broad spectrum of interesting pharmacological properties, ranging from anti-bacterial to anti-cancer activities. There is increasing evidence that ionophores, including salinomycin (SAL), and their semi-synthetic analogues are promising candidates for the development of drugs against parasitic diseases. Our previous studies have shown that esterification and amidation of the C1 carboxylate moiety of SAL provides compounds with potent activity against Trypanosoma brucei, protozoan parasites responsible for African trypanosomiasis. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.061DOI Listing
April 2019
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(±)-trans-Dihydronarciclasine and (±)-trans-dihydrolycoricidine analogues modified in their ring A: Evaluation of their anticancer activity and a SAR study.

Eur J Med Chem 2019 Apr 8;173:76-89. Epub 2019 Apr 8.

Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Budafoki út 8, H-1111, Budapest, Hungary. Electronic address:

A series of (±)-trans-dihydronarciclasine and (±)-trans-dihydrolycoricidine derivatives with variously substituted ring A was synthesised and evaluated for their antiproliferative activity against 60 human tumour cell lines (NCI60), representing leukemia, melanoma, and cancers of the lung, colon, brain, ovary, breast, prostate, as well as kidney in vitro. Among the 13 alkaloids screened, (±)-trans-dihydronarciclasine showed the highest potency as a cytotoxic molecule. A structure-activity relationship (SAR) study indicated that the presence of a hydroxy group at position 7 and a rigid, 1,3-benzodioxole scaffold were essential for the antiproliferative activity. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.04.010DOI Listing
April 2019
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Novel symmetric bis-benzimidazoles: Synthesis, DNA/RNA binding and antitrypanosomal activity.

Eur J Med Chem 2019 Apr 7;173:63-75. Epub 2019 Apr 7.

Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, HR-10000, Zagreb, Croatia. Electronic address:

The novel benzimidazol-2-yl-fur-5-yl-(1,2,3)-triazolyl dimeric series with aliphatic and aromatic central linkers was successfully prepared with the aim of assessing binding affinity to DNA/RNA and antitrypanosomal activity. UV-Visible spectroscopy, thermal denaturation showed interaction of heterocyclic bis-amidines with ctDNA. Circular dichroism studies indicated uniform orientation of heterocyclic bis-amidines along the chiral double helix axis, revealing minor groove binding as the dominant binding mode. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.04.007DOI Listing
April 2019
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Discovery of (R)-5-((5-(1-methyl-1H-pyrazol-4-yl)-4-(methylamino)pyrimidin-2-yl)amino)-3-(piperidin-3-yloxy)picolinonitrile, a novel CHK1 inhibitor for hematologic malignancies.

Eur J Med Chem 2019 Apr 3;173:44-62. Epub 2019 Apr 3.

ZJU-ENS Joint Laboratory of Medicinal Chemistry, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China. Electronic address:

Through virtual screening, we identified the lead compound MCL1020, which exhibited modest CHK1 inhibitory activity. Then a series of 5-(pyrimidin-2-ylamino)picolinonitrile derivatives as CHK1 inhibitors were discovered by further rational optimization. One promising molecule, (R)-17, whose potency was one of the best, had an IC of 0. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.062DOI Listing
April 2019
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3.447 Impact Factor

Development of CXCR4 modulators based on the lead compound RB-108.

Eur J Med Chem 2019 Apr 5;173:32-43. Epub 2019 Apr 5.

Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, USA; Winship Cancer Institute, Emory University, Atlanta, GA, USA. Electronic address:

The CXCR4/CXCL12 axis plays prominent roles in tumor metastasis and inflammation. CXCR4 has been shown to be involved in a variety of inflammation-related diseases. Therefore, CXCR4 is a promising potential target to develop novel anti-inflammatory agents. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.065DOI Listing
April 2019
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Synthesis, and evaluation of in vitro and in vivo anticancer activity of 14-substituted oridonin analogs: A novel and potent cell cycle arrest and apoptosis inducer through the p53-MDM2 pathway.

Eur J Med Chem 2019 Apr 6;173:15-31. Epub 2019 Apr 6.

Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin, 133002, China. Electronic address:

A series of novel oridonin derivatives bearing various substituents on the 14-OH position were designed and synthesised. Their antitumour activity was evaluated in vitro against three human cancer cell lines (HCT116, BEL7402, and MCF7). Most tested derivatives showed improved anti-proliferative activity compared to the lead compound oridonin and the positive control drug 5-fluorouracil (5-Fu). Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.04.005DOI Listing
April 2019
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Design, synthesis and biological evaluation of pyridine-chalcone derivatives as novel microtubule-destabilizing agents.

Eur J Med Chem 2019 Apr 6;173:1-14. Epub 2019 Apr 6.

State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, PR China. Electronic address:

Further optimization of the trimethoxyphenyl scaffold of parent chalcone compound (2a) by introducing a pyridine ring afforded a series of novel pyridine-chalcone derivatives as potential anti-tubulin agents. All the target compounds were evaluated for their antiproliferative activities. Among them, representative compound 16f exhibited the most potent activity with the IC values ranging from 0. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.04.008DOI Listing
April 2019
2 Reads

High affinity CXCR4 inhibitors generated by linking low affinity peptides.

Eur J Med Chem 2019 Jun 1;172:174-185. Epub 2019 Apr 1.

Department of Medicine, Division of Infectious Diseases, School of Medicine, University of California San Diego, La Jolla, CA, 92037, USA. Electronic address:

G-protein coupled receptors (GPCRs) are implicated in many diseases and attractive targets for drug discovery. Peptide fragments derived from protein ligands of GPCRs are commonly used as probes of GPCR function and as leads for drug development. However, these peptide fragments lack the structural integrity of their parent full-length protein ligands and often show low receptor affinity, which limits their research and therapeutic values. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.056DOI Listing
June 2019
1 Read
3.447 Impact Factor

Synthesis and biological evaluation of tryptophan-derived rhodanine derivatives as PTP1B inhibitors and anti-bacterial agents.

Eur J Med Chem 2019 Jun 30;172:163-173. Epub 2019 Mar 30.

Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Yanbian University College of Pharmacy, Yanji, 133000, PR China; College of Medicine, Yanbian University, Yanji, 133000, PR China. Electronic address:

Several series of novel tryptophan-derived rhodanine derivatives were synthesized and identified as potential competitive PTP1B inhibitors and antibacterial agents. Among the compounds studied, 10b was found to have the best in vitro inhibition activity against PTP1B (IC = 0.36 ± 0. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.059DOI Listing

Structure-based modification of carbonyl-diphenylpyrimidines (Car-DPPYs) as a novel focal adhesion kinase (FAK) inhibitor against various stubborn cancer cells.

Eur J Med Chem 2019 Jun 2;172:154-162. Epub 2019 Apr 2.

College of Pharmacy, College of Basic Medical Science, Dalian Medical University, Dalian, 116044, PR China. Electronic address:

A family of carbonyl-substituted diphenylpyrimidine derivatives (Car-DPPYs) with strong activity against focal adhesion kinase (FAK), were described in this manuscript. Among them, compounds 7a (IC = 5.17 nM) and 7f (IC = 2. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.04.004DOI Listing
June 2019
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Third-generation CDK inhibitors: A review on the synthesis and binding modes of Palbociclib, Ribociclib and Abemaciclib.

Eur J Med Chem 2019 Jun 4;172:143-153. Epub 2019 Apr 4.

Department of Pharmaceutical and Pharmacological Sciences, University of Padova, via Marzolo 5, I-35131, Padova, Italy. Electronic address:

The role of cyclin-dependent kinases (CDKs) in regulating the transition of cell cycle steps makes this class of enzymes a suitable target for cancer therapy. Three different generations of CDKs inhibitors have been developed so far. Third-generation compounds (i. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.064DOI Listing

Discovery and optimization of thienopyridine derivatives as novel urea transporter inhibitors.

Eur J Med Chem 2019 Jun 1;172:131-142. Epub 2019 Apr 1.

Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, 100191, PR, China. Electronic address:

Urea transporters (UTs) play an important role in the urine concentrating mechanism and are recognized as novel targets for developing small molecule inhibitors with salt-sparing diuretic activity. Thienoquinoline derivatives, a class of novel UT-B inhibitors identified by our group, play a significant diuresis in animal model. However, the poor solubility and low bioavailability limited its further development. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.060DOI Listing
June 2019
4 Reads
3.447 Impact Factor

Probing structural requirements for human topoisomerase I inhibition by a novel N1-Biphenyl fluoroquinolone.

Eur J Med Chem 2019 Jun 20;172:109-130. Epub 2019 Mar 20.

Division of Medicinal and Natural Products Chemistry, Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, 115 S Grand Ave., S321 Pharmacy Building, Iowa City, IA, 52242, USA. Electronic address:

Fluoroquinolones substituted with N-1 biphenyl and napthyl groups were discovered to act as catalytically inhibitors of human topoisomerases I and II, and to possess anti-proliferative activity in vivo. Structural requirements for these novel quinolones to inhibit catalytic activity of human topoisomerase I have not been explored. In this work novel derivatives of the N-1 biphenyl fluoroquinolone were designed, synthesized and evaluated to understand structural requirements of the C-3 carboxylic acid, C-6 fluorine, C-7 aminomethylpyrrolidine, C-8 methoxy, and the N-1 biphenyl functional groups for hTopoI inhibition. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.040DOI Listing
June 2019
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PIM kinase inhibitors: Structural and pharmacological perspectives.

Eur J Med Chem 2019 Jun 23;172:95-108. Epub 2019 Mar 23.

Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur, 495009, Chhattisgarh, India. Electronic address:

The PIM kinase, also known as serine/threonine kinase plays an important role in cancer biology and is found in three different isoforms namely PIM-1, PIM-2, and PIM-3. They are extensively distributed and are implicated in a variety of biological processes, including cell proliferation, cell differentiation, and apoptosis. They act as weak oncogene and whenever expressed in exacerbating forms are responsible for different types of human cancer. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.050DOI Listing
June 2019
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Anti-tubulin agents of natural origin: Targeting taxol, vinca, and colchicine binding domains.

Eur J Med Chem 2019 Jun 14;171:310-331. Epub 2019 Mar 14.

Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Reseach, Jamia Hamdard, New Delhi, India.

Microtubules are a protein which is made of α- and β-heterodimer. It is one of the main components of the cell which play a vital role in cell division especially in G2/M-phase. It exists in equilibrium dynamic of polymerization and depolymerization of α- and β-heterodimer. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.025DOI Listing
June 2019
2 Reads

Modulation of the spacer in N,N-bis(alkanol)amine aryl ester heterodimers led to the discovery of a series of highly potent P-glycoprotein-based multidrug resistance (MDR) modulators.

Eur J Med Chem 2019 Jun 27;172:71-94. Epub 2019 Mar 27.

Department of Neuroscience, Psychology, Drug Research and Child's Health - Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, via Ugo Schiff 6, 50019 Sesto Fiorentino (FI), Italy.

In this study, a new series of N,N-bis(alkanol)amine aryl ester heterodimers was synthesized and studied. The new compounds were designed based on the structures of our previous arylamine ester derivatives endowed with high P-gp-dependent multidrug resistance reversing activity on a multidrug-resistant leukemia cell line. All new compounds were active in the pirarubicin uptake assay on the doxorubicin-resistant erythroleukemia K562 cells (K562/DOX). Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.054DOI Listing
June 2019
3 Reads

Thiophenol-formaldehyde triazole causes apoptosis induction in ovary cancer cells and prevents tumor growth formation in mice model.

Eur J Med Chem 2019 Jun 20;172:62-70. Epub 2019 Mar 20.

Department of Gynaecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China. Electronic address:

In the present study a library of thiophenol-formaldehyde-triazole (TFT) derivatives was synthesized and screened against CAOV3, CAOV4 and ES-2 ovary cancer cell lines. Initial screening revealed that five-compounds 5a, 5b, 5j, 5h and 5i inhibited the viability of tested cell lines. Analysis of apoptosis revealed that increase in compound 5a (most active) concentration from 0. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.033DOI Listing
June 2019
6 Reads

Exploring the PROTAC degron candidates: OBHSA with different side chains as novel selective estrogen receptor degraders (SERDs).

Eur J Med Chem 2019 Jun 26;172:48-61. Epub 2019 Mar 26.

State Key Laboratory of Virology, Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, China. Electronic address:

As the mutant estrogen receptor (ER) continues to be characterized, breast cancer is becoming increasingly difficult to cure when treated with hormone therapy. In this regard, a strategy to selectively and effectively degrade the ER might be an effective alternative to endocrine therapy for breast cancer. In a previous study, we identified a novel series of 7-oxabicyclo[2. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.058DOI Listing
June 2019
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2,4-Disubstituted quinazolines targeting breast cancer cells via EGFR-PI3K.

Eur J Med Chem 2019 Jun 17;172:36-47. Epub 2019 Mar 17.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, 450001, PR China. Electronic address:

A series of novel 2,4-disubstituted quinazolines were synthesized and evaluated for their anti-tumor activity against five human cancer cells (MDA-MB-231, MCF-7, PC-3, HGC-27 and MGC-803) using MTT assay. Among them, compound 9n showed the most potent cytotoxicity against breast cancer cells. Compound 9n also significantly inhibited the colony formation and migration of MDA-MB-231 and MCF-7 cells. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S02235234193024
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http://dx.doi.org/10.1016/j.ejmech.2019.03.030DOI Listing
June 2019
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Anti-PqsR compounds as next-generation antibacterial agents against Pseudomonas aeruginosa: A review.

Eur J Med Chem 2019 Jun 25;172:26-35. Epub 2019 Mar 25.

Department of Pharmaceutical Control, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Institute, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Nowadays, due to spreading antibiotic resistance among clinically relevant pathogens, the requirement of novel therapeutic approaches is felt more than ever. One of the alternative strategies is anti-virulence therapy without affecting bacterial growth or viability. In Pseudomonas aeruginosa, an opportunistic human pathogen that exhibits intrinsic multi-drug resistance, both virulence factors' production and biofilm formation depends on its quorum sensing (QS) network. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.049DOI Listing
June 2019
3 Reads

Targeting gliomas with triazene-based hybrids: Structure-activity relationship, mechanistic study and stability.

Eur J Med Chem 2019 Jun 22;172:16-25. Epub 2019 Mar 22.

Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal. Electronic address:

Herein we report novel hybrid compounds based on valproic acid and DNA-alkylating triazene moieties, 1, with therapeutic potential for glioblastoma multiforme chemotherapy. We identified hybrid compounds 1d and 1e to be remarkably more potent against glioma and more efficient in decreasing invasive cell properties than temozolomide and endowed with chemical and plasma stability. In contrast to temozolomide, which undergoes hydrolysis to release an alkylating metabolite, the valproate hybrids showed a low potential to alkylate DNA. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.048DOI Listing
June 2019
4 Reads

Structural optimization on a virtual screening hit of smoothened receptor.

Eur J Med Chem 2019 Jun 26;172:1-15. Epub 2019 Mar 26.

Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, 215123, PR China. Electronic address:

The Hedgehog (Hh) pathway plays a critical role during embryonic development by controlling cell patterning, growth and migration. In adults, the function of Hh pathway is curtailed to tissue repair and maintenance. Aberrant reactivation of Hh signaling has been linked to tumorigenesis in various cancers, such as basal cell carcinoma (BCC) and medulloblastoma. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.057DOI Listing
June 2019
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Caprazamycins: Promising lead structures acting on a novel antibacterial target MraY.

Eur J Med Chem 2019 Jun 20;171:462-474. Epub 2019 Mar 20.

School of Pharmacy and Pharmacology, Griffith University, Gold Coast, QLD, 4222, Australia; Quality Use of Medicines Network, Gold Coast, QLD, 4222, Australia. Electronic address:

The present status of antibiotic resistant requires an urgent invention of novel agents that act on clinically unexplored antibacterial targets. The enzyme MraY (phospho-MurNAc-pentapeptide translocase), essential for bacterial cell wall synthesis, fulfils this criterion as it has not been explored as a target in a clinical context. Specifically, the enzyme is involved in the lipid-linked cycle of peptidoglycan biosynthesis and is reportedly targeted by naturally-occurring nucleoside antibiotics. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.01.071DOI Listing
June 2019
2 Reads

GABA allosteric modulators: An overview of recent developments in non-benzodiazepine modulators.

Eur J Med Chem 2019 Jun 23;171:434-461. Epub 2019 Mar 23.

Faculty of Pharmacy, The University of Sydney, Camperdown Campus, Sydney, Australia. Electronic address:

γ-Aminobutyric acid (GABA) is the major inhibitory transmitter controlling synaptic transmission and neuronal excitability. It is present in a high percentage of neurons in the central nervous system (CNS) and also present in the peripheral nervous system, and acts to maintain a balance between excitation and inhibition. GABA acts via three subclasses of receptors termed GABA, GABA, and GABA. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.043DOI Listing
June 2019
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Structure-activity relationship studies of (E)-3,4-dihydroxystyryl alkyl sulfones as novel neuroprotective agents based on improved antioxidant, anti-inflammatory activities and BBB permeability.

Eur J Med Chem 2019 Jun 21;171:420-433. Epub 2019 Mar 21.

Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China. Electronic address:

(E)-3,4-dihydroxystyryl alkyl sulfones, as new analogues of neurodegenerative agents, were designed and synthesized. The biological results demonstrated that most of the target compounds preserved antioxidant and anti-inflammatory potency in scavenging reactive free radicals, protecting neuronal cells against neurotoxins such as HO, 6-hydroxydopamine and inhibiting lipopolysaccharide (LPS)-induced over-production of NO. Among these compounds, 6. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.044DOI Listing
June 2019
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Stereoselective synthesis and biological evaluation as inhibitors of hepatitis C virus RNA polymerase of GSK3082 analogues with structural diversity at the 5-position.

Eur J Med Chem 2019 Jun 12;171:401-419. Epub 2019 Mar 12.

Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), CSIC - Universidad de Zaragoza, Departamento de Química Orgánica, Pedro Cerbuna 12, 50009 Zaragoza, Spain. Electronic address:

GSK3082 - a hepatitis C virus RNA polymerase inhibitor - and a series of analogues with structural diversity at the 5-position were prepared from a 2,2,4,5-tetrasubstituted pyrrolidine obtained with a well-defined stereochemistry from the 1,3-dipolar cycloaddition of the chiral imino ester derived from leucine tert-butyl ester and (R)-2,3-O-isopropylideneglyceraldehyde with methyl acrylate. The chiral 2,2-dimethyl-1,3-dioxolane moiety provided by the glyceraldehyde served as a synthetic equivalent for different substituents and functional groups and these transformations usually required mild reaction conditions and simple work-up procedures. The inhibitory activity of the resulting GSK3082 analogues was studied in vitro in a cell-based assay of the subgenomic HCV RNA replication system. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.019DOI Listing
June 2019
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PRODRUGS FOR NITROREDUCTASE BASED CANCER THERAPY- 2: Novel amide/Ntr combinations targeting PC3 cancer cells.

Eur J Med Chem 2019 Jun 23;171:383-400. Epub 2019 Mar 23.

Department of Chemistry, Faculty of Sciences and Arts, Natural Products and Drug Research Laboratory, Çanakkale Onsekiz Mart University, Çanakkale, 17020, Turkey. Electronic address:

The use of nitroreductases (NTR) that catalyze the reduction of nitro compounds by using NAD(P)H in GDEPT (Gene-directed enzyme prodrug therapy) studies which minimize toxicity at healthy cells and increases concentration of drugs at cancer cells is remarkable. Discovery of new prodrug/NTR combinations is necessary to be an alternative to known prodrug candidates such as CB1954, SN23862, PR-104A. For this aim, nitro containing aromatic amides (A1-A23) were designed, synthesized, performed in silico ADMET and molecular docking techniques in this study. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.035DOI Listing
June 2019
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Novel benzenesulfonamide and 1,2-benzisothiazol-3(2H)-one-1,1-dioxide derivatives as potential selective COX-2 inhibitors.

Eur J Med Chem 2019 Jun 20;171:372-382. Epub 2019 Mar 20.

Pharmaceutical Chemistry Department, Faculty of Pharmacy, Taif University, 11099, Taif, Saudi Arabia; Medicinal Chemistry Department, Faculty of Pharmacy, Zagazig University, 44519, Zagazig, Egypt.

Two new series of 1,2-benzisothiazol-3(2H)-one-1,1-dioxide derivatives containing either five membered heterocyclic rings or aryl hydrazones were synthesized and evaluated for their in vitro COX-1/COX-2 inhibitory activity. In vivo anti-inflammatory evaluation revealed that benzenesulfonamides bearing pyrazole moiety 19, 20 and its cyclized form 23 exhibited the highest anti-inflammatory activity with comparable potency to celecoxib. Furthermore, the ulcerogenic activity evaluation showed that compounds 19, 20 and 23 exerted the minimal ulcer index in comparison to indomethacin as a reference drug. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.042DOI Listing
June 2019
2 Reads

Synthesis of sulfamethoxazole and sulfabenzamide metal complexes; evaluation of their antibacterial activity.

Eur J Med Chem 2019 Jun 21;171:364-371. Epub 2019 Mar 21.

Department of Microbial Biotechnology, School of Biology, College of Science, University of Tehran, Enghelab Avenue, Tehran, 14155-6655, Iran. Electronic address:

The present work describes the synthesis and spectroscopic characterization of ten different metal complexes of sulfabenzamide and sulfamethoxazole as ligands (M-SBZ, M-SMZ). Spectroscopic methods such as H NMR, UV-Vis spectroscopy analysis, FTIR and XRD confirmed the coordination of both ligands to metals through the nitrogen and oxygen atoms of the sulfonamide group. Both sulfabenzamide and sulfamethoxazole metal complexes were active against Gram-positive and negative bacterial strains. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.002DOI Listing
June 2019
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The peculiarities of cancer cell metabolism: A route to metastasization and a target for therapy.

Eur J Med Chem 2019 Jun 23;171:343-363. Epub 2019 Mar 23.

CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal. Electronic address:

The last decade has witnessed the peculiarities of metabolic reprogramming in tumour onset and progression, and their relevance in cancer therapy. Also, it has been indicated that the metastatic process may depend on the metabolic rewiring and adaptation of cancer cells to the pressure of tumour microenvironment and limiting nutrient availability. The present review gatherers the existent knowledge on the influence of tumour microenvironment and metabolic routes driving metastasis. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.053DOI Listing
June 2019
2 Reads
3.447 Impact Factor

New pyrazole derivatives: Synthesis, anti-inflammatory activity, cycloxygenase inhibition assay and evaluation of mPGES.

Eur J Med Chem 2019 Jun 23;171:332-342. Epub 2019 Mar 23.

Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr Elini St., Cairo 11562, Egypt; Pharmaceutical Chemistry Department, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt.

New pyrazole derivatives 2-5 were synthesized and evaluated for their COX-1 and COX-2 inhibitory activity in vitro. All compounds showed good inhibitory activity at a nanomolar level and most compounds exhibited selectivity towards COX-2 inhibition. Compounds 2a, 3b, 4a, 5b and 5e exhibited IC towards COX-2 enzyme of 19. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.052DOI Listing

Discovery of novel mutant-combating ALK and ROS1 dual inhibitors bearing imidazolidin-2-one moiety with reasonable PK properties.

Eur J Med Chem 2019 Jun 23;171:297-309. Epub 2019 Mar 23.

Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China. Electronic address:

Aiming to identify novel potent ALK and ROS1 dual inhibitors, the relatively bulky piperidine fragment in ceritinib was replaced with substituted imidazolidin-2-one moiety which gave rise to a series of 2,4-diaryl-aminopyrimidine (DAAP) analogs (6-33). SAR studies were conducted based on cellular assays on five cell lines and most compounds exerted moderated to excellent activities. Among them, 15 showed excellent inhibitory activities against ROS1 and ALK positive cell lines, especially Ba/F3, with IC values ranging from 14 to 37 nM. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.038DOI Listing
June 2019
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Design, synthesis and biological evaluation of novel uracil derivatives bearing 1, 2, 3-triazole moiety as thymidylate synthase (TS) inhibitors and as potential antitumor drugs.

Eur J Med Chem 2019 Jun 24;171:282-296. Epub 2019 Mar 24.

School of Pharmacy, China Medical University, Shenyang, 110122, PR China. Electronic address:

Research on thymidylate synthase inhibitors has been a hot spot for anticancer drug development. Here, based on the structures and pharmacological properties of two types of TS inhibitors, through a molecular assembly principle of drugs design, we designed and synthesized a series of 30 novel uracil derivatives as TS inhibitors. The antiproliferative ability of these compounds was evaluated against four cancer cell lines (A549, OVCAR-3, SGC-7901, and HepG2) by the MTT assay. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.047DOI Listing
June 2019
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Discovery and biological evaluation of novel androgen receptor antagonist for castration-resistant prostate cancer.

Eur J Med Chem 2019 Jun 22;171:265-281. Epub 2019 Mar 22.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China; Hinova Pharmaceuticals Inc, 4th Floor, Building RongYao A, No. 5, Keyuan South Road, Chengdu, 610041, China. Electronic address:

Prostate cancer (PC) is the second most common malignancy in men worldwide. Among current therapies, two antiandrogens, Abiraterone Acetate and Enzalutamide (Enza) have become the standard of care for patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we designed and synthesized a new series of nonsteroidal compounds deriving from the hybridization of Abiraterone (Abi) and Enzalutamide, among which compound 4a featuring the diphenylamine scaffold was identified as a potent and cell selective androgen receptor (AR) antagonist. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.041DOI Listing
June 2019
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Naphthyl quinoxaline thymidine conjugate is a potent anticancer agent post UVA activation and elicits marked inhibition of tumor growth through vaccination.

Eur J Med Chem 2019 Jun 23;171:255-264. Epub 2019 Mar 23.

Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China. Electronic address:

Anticancer anthracyclines are cytotoxic drugs that can induce antitumor immune response as a secondary effect through immunogenic cell death (ICD) mechanism. However, the immunogenic potency is quite limited, possibly due to that these chemotherapeutic agents are not specifically developed as ICD inducers. Thus, new drug entities through studies focusing on enhanced ICD induction would significantly promote antitumor immune response in the vaccination application. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.03.051DOI Listing
June 2019
1 Read
3.447 Impact Factor