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PubMed Journal Database | European journal of medicinal chemistry RSS

06:54 EDT 24th May 2019 | BioPortfolio

The US National Library of Medicine and National Institutes of Health manage PubMed.gov which comprises of more than 29 million records, papers, reports for biomedical literature, including MEDLINE, life science and medical journals, articles, reviews, reports and  books.

BioPortfolio aims to cross reference relevant information on published papers, clinical trials and news associated with selected topics - speciality.

For example view all recent relevant publications on Epigenetics and associated publications and clincial trials.

Showing PubMed Articles 1–25 of 1,900+ from European journal of medicinal chemistry

Multi-targeting protein-protein interaction inhibitors: Evolution of macrocyclic ligands with embedded carbohydrates (MECs) to improve selectivity.

Compounds targeting multiple proteins can have synergistic effects and are therefore of interest in medicinal chemistry. At the same time, inhibiting protein-protein interactions (PPI) is increasingly desired in the treatment of disorders or diseases. The development of non-peptidomimetic inhibitors is still a challenge. Herein we investigate macrocyclic scaffolds with one or two embedded carbohydrates (MECs) that present amino acid side chains, or related isosteres, as pharmacophoric groups. Firstly, retro...

1,3-Dioxane as a scaffold for potent and selective 5-HTR agonist with in-vivo anxiolytic, anti-depressant and anti-nociceptive activity.

A series of compounds generated by ring expansion/opening and molecular elongation/simplification of the 1,3-dioxolane scaffold were prepared and tested for binding affinity at 5-HTR and α adrenoceptors. The compounds with greater affinity were selected for further functional studies. N-((2,2-diphenyl-1,3-dioxan-5-yl)methyl)-2-(2-methoxyphenoxy)ethan-1-ammonium hydrogen oxalate (12) emerged as highly potent full agonist at the 5-HTR (pKi 5-HT = 8.8; pD = 9.22, %E = 92). The pharmacokinetic data...

An update about the crucial role of stereochemistry on the effects of Peroxisome Proliferator-Activated Receptor ligands.

Peroxisome Proliferator-Activated Receptors (PPARs) are ligand-activated transcription factors that govern lipid and glucose homeostasis playing a central role in cardiovascular disease, obesity, and diabetes. These receptors show a high degree of stereoselectivity towards several classes of drugs. This review covers the most relevant findings that have been made in the last decade and takes into consideration only those compounds in which stereochemistry led to unexpected results or peculiar interactions w...

Synthetic heterocyclic candidates as promising α-glucosidase inhibitors: An overview.

α-Glucosidase enzyme inhibition is an effective therapeutic decorum in the treatment of type 2 diabetes mellitus. Since 1990, three α-glucosidase inhibitors are known to exist clinically, Acarbose, Voglibose and Miglitol. Side effects and long synthetic routes to access them forced the researchers to move their focus to discover simple and small heterocyclic motifs that work as promising α-glucosidase inhibitors and may eventually lead to the management of postprandial hyperglycemic condition in T2DM. In...

Synthesis and biological evaluation of novel xanthine derivatives as potential apoptotic antitumor agents.

A series of novel xanthine/NO donor hybrids containing 1,3,8-trisubstituted or 1,8-disubstituted xanthine derivatives were designed and synthesized. The synthesized compounds were tested in a cell viability assay using human mammary gland epithelial cell line (MCF-10A) where all the compounds exhibited no cytotoxic effects and more than 90% cell viability at a concentration of 50 μM. The oxime containing compounds 7a-b and 17-24 were more active as antiproliferative agents than their non-oxime congeners ...

Phytochemical and pharmacological attributes of piperine: A bioactive ingredient of black pepper.

Plants are vital for the wellbeing of humankind in a variety of ways. Some plant extracts contain antimicrobial properties that can treat different pathogens. Most of the world's population relies on medicinal plants and natural products for their primary health care needs. Therefore, there is a growing interest in natural products, medicinal plants, and traditional medicine along with a desire to design and develop novel plant-based pharmaceuticals. These plant-based pharmaceuticals may address the concern...

Dehydrodieugenol B derivatives as antiparasitic agents: Synthesis and biological activity against Trypanosoma cruzi.

Chagas disease is a neglected protozoan disease that affects more than eight million people in developing countries. Due to the limited number and toxicity profiles of therapies in current use, new drugs are urgently needed. In previous studies, we reported the isolation of two related antitrypanosomal neolignans from Nectandra leucantha (Lauraceae). In this work, a semi-synthetic library of twenty-three neolignan derivatives was prepared to explore synthetically accessible structure activity relationships ...

Optically pure chiral copper(II) complexes of rosin derivative as attractive anticancer agents with potential anti-metastatic and anti-angiogenic activities.

The development of optically pure drugs is the trend of new drugs research. Searching for optically pure metallodrugs against cancer has not been taken seriously. [CuLCl]Cl·2CHCl·HO (1) and [CuLBr]Br·2CHCl (2) (L = 2-amino-5-dehydroabietyl-1,3,4-thiadiazole), two rosin-derivative based optically pure chiral copper(II) complexes, are rationally synthesized as potential anticancer agents. 1 exhibits effective in vitro and in vivo anticancer activities and tolerable toxicities. 1 promotes MCF-7 cell de...

Synthesis and structure-activity relationships of small-molecular di-basic esters, amides and carbamates as flaviviral protease inhibitors.

Inhibitors of the flaviviral serine proteases, which are crucial for the replication of dengue and West-Nile virus, have attracted much attention over the last years. A dibasic 4-guanidinobenzoate was previously reported as inhibitor of the dengue protease with potency in the low-micromolar range. In the present study, this lead structure was modified with the intent to explore structure-activity relationships and obtain compounds with increased drug-likeness. Substitutions of the guanidine moieties, the ar...

Thioether-based 2-aminobenzamide derivatives: Novel HDAC inhibitors with potent in vitro and in vivo antitumor activity.

Previously, we focused on a series of 2-aminobenzamide-based histone deacetylase (HDAC) inhibitors, compound 9 of which displayed potent HDAC inhibitory activity against HDAC1 and HDAC2, and moderate anti-proliferative activity against several cancer cell lines. In the current study, we have designed and synthesized a series of novel HDAC inhibitors based on thioether moiety with 9 as a lead compound. Representative compounds12 g and 12 h showed apparently potent anti-proliferative activities against fi...

Salinomycin and its derivatives - A new class of multiple-targeted "magic bullets".

The history of drug development clearly shows the scale of painstaking effort leading to a finished product - a highly biologically active agent that would be at the same time no or little toxic to human organism. Moreover, the aim of modern drug discovery can move from "one-molecule one-target" concept to more promising "one-molecule multiple-targets" one, particularly in the context of effective fight against cancer and other complex diseases. Gratifyingly, natural compounds are excellent source of potent...

Multi-target design strategies for the improved treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial syndrome resulting in profound misery and poses a substantial burden on human health, economy, and society throughout the world. Based on the numerous AD-related targets in the disease network, multi-target design strategy is a crucial direction to seek for enhanced therapy, and multi-target drugs have the ability to regulate more targets than single-target drugs, affecting the disease network with more potency. Herein, we highlight nine major targets associated ...

Combining structure- and property-based optimization to identify selective FLT3-ITD inhibitors with good antitumor efficacy in AML cell inoculated mouse xenograft model.

FLT3 mutation is among the most common genetic mutations in acute myeloid leukemia (AML), which is also related with poor overall survival and refractory in AML patients. Recently, FLT3 inhibitors have been approved for AML therapy. Herein, a series of new compounds with pyrazole amine scaffold was discovered, which showed potent inhibitory activity against FLT3-ITD and significant selectivity against both FLT3-ITD and AML cells expressing FLT3-ITD. Compound 46, possessing the most promising cellular activi...

Natural products as multidrug resistance modulators in cancer.

Cancer is a prominent cause of death globally. Currently, many drugs that are in clinical practice are having a high prevalence of side effect and multidrug resistance. Risk of tumors acquiring resistance to chemotherapy (multidrug resistance) remains a significant hurdle to the successful treatment of various types of cancer. Membrane-embedded drug transporters, generally overexpressed in cancer, are the leading cause among multiple mechanisms of multidrug resistance (MDR). P-glycoprotein (P-gp) also MDR1/...

Development, synthesis, and Ga-Labeling of a Lipophilic complexing agent for atherosclerosis PET imaging.

Cardiovascular disease is the leading cause of mortality and morbidity worldwide. Atherosclerosis accounts for 50% of deaths in western countries. This multifactorial pathology is characterized by the accumulation of lipids and inflammatory cells within the vascular wall, leading to plaque formation. We describe herein the synthesis of a PCTA-based Ga chelator coupled to a phospholipid biovector 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE), which is the main constituent of the phospholipid moiety ...

Discovery of chalcone-modified estradiol analogs as antitumour agents that Inhibit tumour angiogenesis and epithelial to mesenchymal transition.

Angiogenesis plays an essential role in tumourigenesis and tumour progression, and anti-angiogenesis therapies have shown promising antitumour effects in solid tumours. 2-Methoxyestradiol (2ME2), an endogenous metabolite of estradiol, has been regarded as a potential antitumour agent mainly targeting angiogenesis. Here we synthesized a novel series of chalcones based on 2-methoxyestradiol and evaluated their potential activities against tumours. Compound 11e was demonstrated to have potent antiangiogenic ac...

Sequence modification of heptapeptide selected by phage display as homing device for HT-29 colon cancer cells to improve the anti-tumour activity of drug delivery systems.

Development of peptide-based conjugates for targeted tumour therapy is a current research topic providing new possibilities in cancer treatment. In this study, VHLGYAT heptapeptide selected by phage display technique for HT-29 human colon cancer was investigated as homing peptide for drug delivery. Daunomycin was conjugated to the N-terminus of the peptide directly or through Cathepsin B cleavable spacers. Conjugates showed moderate in vitro cytostatic effect. Therefore, sequence modifications were perform...

The past, present and future of potential small-molecule drugs targeting p53-MDM2/MDMX for cancer therapy.

The p53 gene, a well-known tumor suppressor gene, plays a crucial role in cell cycle regulation, DNA repair, cell differentiation, and apoptosis. MDM2 exerts p53-dependent activity mainly by binding to p53 protein to form MDM2-p53 negative feedback loop. In addition, MDM2 is involved in a number of pathways that regulate cell proliferation and apoptosis, playing a p53-independent role. The p53 binding domain of MDMX bind to p53 transcriptional activation domain, inhibiting the transcriptional activity of p5...

New chalcone-sulfonamide hybrids exhibiting anticancer and antituberculosis activity.

New sulfonamides 5/6 derived from 4-methoxyacetophenone 1 were synthesized by N-sulfonation reaction of ammonia (3) and aminopyrimidinone (4) with its sulfonyl chloride derivative 2. Sulfonamides 5 and 6 were used as precursors of two new series of chalcones 8a-f and 9a-f, which were obtained through Claisen-Schmidt condensation with aromatic aldehydes 7a-f. Compounds 5/6, 8a-d, 8f, 9a-d, and 9f were screened by the US National Cancer Institute (NCI) at 10 μM against sixty different human cancer cell lin...

Ursolic acid derivative induces apoptosis in glioma cells through down-regulation of cAMP.

The present study was designed to synthesize and evaluate ursolic acid hybrid compounds against glioma cells. Initial screening revealed that most of the synthesized compounds displayed better inhibitory effect on glioma cell proliferation compared to parent ursolic acid. The mechanism of inhibitory effect of the most potent compound 6d on glioma cells was investigated in detail. Treatment with compound 6d significantly (p 

Therapeutic potential of natural compounds in inflammation and chronic venous insufficiency.

The term varicose vein refers to the twisted and swollen vein visible under the skin surface which occurs most commonly in the leg. Epidemiological studies report a varying percentage of incidences from 2 to 56% in men and

Development and future prospects of selective organometallic compounds as anticancer drug candidates exhibiting novel modes of action.

Organometallic complexes have widely been used for the treatment of various diseases viz., malaria, arthritis, syphilis, pernicious anemia, tuberculosis and particular in cancers. Recent decades have witnessed an upsurging interest in the application of organometallic compounds to treat various phenotypes of cancers with multiple etiologies. The unique and exceptional properties of organometallic compounds, intermediate between classical inorganic and organic materials provide new insight in the progress of...

Synthesis and evaluation of new quinazolin-4(3H)-one derivatives as potent antibacterial agents against multidrug resistant Staphylococcus aureus and Mycobacterium tuberculosis.

Staphylococcus aureus and Mycobacterium tuberculosis are major causative agents responsible for serious nosocomial and community-acquired infections impacting healthcare systems globally. Over several decades, these pathogens have developed resistance to multiple antibiotics significantly affecting morbidity and mortality. Thus, these recalcitrant pathogens are amongst the most formidable microbial pathogens for which international healthcare agencies have mandated active identification and development of n...

Pyridinylimidazoles as dual glycogen synthase kinase 3β/p38α mitogen-activated protein kinase inhibitors.

Compounds simultaneously inhibiting two targets that are involved in the progression of the same complex disease may exhibit additive or even synergistic therapeutic effects. Here we unveil 2,4,5-trisubstituted imidazoles as dual inhibitors of p38α mitogen-activated protein kinase and glycogen synthase kinase 3β (GSK3β). Both enzymes are potential therapeutic targets for neurodegenerative disorders, like Alzheimer's disease. A set of 39 compounds was synthesized and evaluated in kinase activity assays fo...

Structure-guided optimization of 4,6-substituted-1,3,5-triazin-2(1H)-ones as catalytic inhibitors of human DNA topoisomerase IIα.

Human DNA topoisomerases represent one of the key targets of modern chemotherapy. An emerging group of catalytic inhibitors of human DNA topoisomerase IIα comprises a new paradigm directed to circumvent the known limitations of topoisomerase II poisons such as cardiotoxicity and induction of secondary tumors. In our previous studies, 4,6-substituted-1,3,5-triazin-2(1H)-ones were discovered as catalytic inhibitors of topo IIα. Here, we report the results of our efforts to optimize several properties of the...


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