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PubMed Journal Database | Future medicinal chemistry RSS

18:12 EST 11th December 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.

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

Showing PubMed Articles 1–25 of 96 from Future medicinal chemistry

Recent advances in transmission-blocking drugs for malaria elimination.

The scientific community worldwide has realized that malaria elimination will not be possible without development of safe and effective transmission-blocking interventions. Primaquine, the only WHO recommended transmission-blocking drug, is not extensively utilized because of the toxicity issues in G6PD deficient individuals. Therefore, there is an urgent need to develop novel therapeutic interventions that can target malaria parasites and effectively block transmission. But at first, it is imperative to un...

Public resources for chemical probes: the journey so far and the road ahead.

High-quality small molecule chemical probes are extremely valuable for biological research and target validation. However, frequent use of flawed small-molecule inhibitors produces misleading results and diminishes the robustness of biomedical research. Several public resources are available to facilitate assessment and selection of better chemical probes for specific protein targets. Here, we review chemical probe resources, discuss their current strengths and limitations, and make recommendations for furt...

A dual functional probe for assessing human CYP450 3A5 and 3A enzymes bioactivities.

CYP3A5 plays a vital role in the drug metabolism, it displays varied expression levels among individuals and is easily influenced by genetic polymorphisms and some diseases. A dual function probe isobutyryl-11-keto--boswellic acid (IKBA) was developed; it possessed a high selectivity toward CYP3A5 and CYP3A enzymes for its two individual metabolites, respectively. The probe has the high accuracy and wide applicability in measuring the real activity of CYP3A5. Finally, IKBA was successfully used for the eva...

The importance of amide protons in peptide drug development.

Triazol: a privileged scaffold for proteolysis targeting chimeras.

Current traditional drugs such as enzyme inhibitors and receptor agonists/antagonists present inherent limitations due to occupancy-driven pharmacology as the mode of action. Proteolysis targeting chimeras (PROTACs) are composed of an E3 ligand, a connecting linker and a target protein ligand, and are an attractive approach to specifically knockdown-targeted proteins utilizing an event-driven mode of action. The length, hydrophilicity and rigidity of connecting linkers play important role in creating a succ...

Epigenetic drug discovery: systematic assessment of chemical space.

The druggability of epigenetic targets has prompted researchers to develop small-molecule therapeutics. However, no systematic assessment has ever been done to investigate the chemical space of epigenetic modulators. Herein, we report a comprehensive chemoinformatic analysis of epigenetic ligands from EpiDBase, HEMD, ChEMBL and PubChem databases. Nearly, 0.45 × 10 ligands were analyzed for assay interference compounds, target profiling, drug-like properties and hit prioritization. After eliminating approx...

Design, synthesis and evaluation of belinostat analogs as histone deacetylase inhibitors.

Histone deacetylase (HDAC) is an attractive target for antitumor therapy. Therefore, the development of novel HDAC inhibitors is warranted. A series of HDAC inhibitors based on -hydroxycinnamamide fragment was designed as the clinically used belinostat analog using amide as the connecting unit. All target compounds were evaluated for their HDAC inhibitory activities and some selected compounds were tested for their antiproliferative activities. Among them, compound showed an IC value of 11.5 nM in inhi...

Ruthenium dendrimers against acute promyelocytic leukemia:  studies on HL-60 cells.

Coordination of ruthenium arene fragments on carbosilane dendrimers' surface greatly increases their antitumor properties. Newly synthetized ruthenium dendrimers are water-soluble, monodisperse and stable. Since carbosilane dendrimers are good carriers of drugs and genes, the presence of ruthenium in their structure makes them promising candidates for new drug delivery systems with improved antitumor potential. Carbosilane ruthenium dendrimers are more toxic to cancer cells than normal cells. Results of sev...

NMR investigation of protein-ligand interactions for G-protein coupled receptors.

In this review, we report NMR studies of ligand-GPCR interactions, including both ligand-observed and protein-observed NMR experiments. Published studies exemplify how NMR can be used as a powerful tool to design novel GPCR ligands and investigate the ligand-induced conformational changes of GPCRs. The strength of NMR also lies in its capability to explore the diverse signaling pathways and probe the allosteric modulation of these highly dynamic receptors. By offering unique opportunities for the identifica...

Neural networks in drug discovery: current insights from medicinal chemists.

The progresses in curcuminoids-based metal complexes: especially in cancer therapy.

Curcuminoids (CURs), a series of derivatives in turmeric (), are commonly discovered to control the deterioration of cancers. However, the physiochemical properties and the original side effects of many CURs complexes put barriers in their medical applications. To address them, the investigation of metal-based complexes with CURs is in progress. The complexes were summarized according to articles in recent years. The results showed that the complexes improved the physicochemical properties or therapeutic pe...

Translational role of natural coumarins and their derivatives as anticancer agents.

Natural coumarins and their derivatives isolated from various plants or microorganisms have inherent antioxidant, antibacterial, antifungal, antiviral and anticancer properties among many biological activities. Some of these coumarins and their derivatives lead to self-programmed cancer cell death (apoptosis) via different mechanisms, which will be discussed. The link between bacterial and viral infections to cancer compels us to highlight fascinating reports from coumarin isolation from microorganisms;...

Cyclohexyl amide-based novel bacterial topoisomerase inhibitors with prospective GyrA-binding fragments.

Novel bacterial topoisomerase inhibitors (NBTIs) are a promising class of bacterial topoisomerase II inhibitors that are gaining more and more importance mainly because of their excellent antibacterial activity, as well as their lack of cross-resistance to quinolones. Described here is the synthesis and biological evaluation of a tiny series of new virtually assembled NBTIs containing synthetically feasible right-hand side fragments capable of binding the GyrA subunit of the bacterial DNA gyrase-DNA comple...

KRAS inhibitors on the horizon.

Toward understanding calmodulin plasticity by molecular dynamics.

Calmodulin interacts in many different ways with its ligands. We aim to shed light on its plasticity analyzing the changes followed by the linker region and the relative position of the lobes using conventional molecular dynamics, accelerated MD and scaled MD (sMD). Three different structures of calmodulin are compared, obtaining a total of 2.5 μs of molecular dynamics, which have been analyzed using the principal component analysis and clustering methodologies. sMD simulations reach conformations that...

Identification of novel monoamine oxidase selective inhibitors employing a hierarchical ligand-based virtual screening strategy.

Due to the pivotal role in the oxidative deamination of monoamine neurotransmitters, two distinct monoamine oxidase (MAO) subtypes, MAO-A and MAO-B, present a significant pharmacological interest. Here, we reported a hierarchical and time-efficient ligand-based virtual screening strategy to identify potent selective and reversible MAO inhibitors. A total of 130 compounds were assessed in dose-response biochemical assay against MAOs. Among them, 70 compounds were active with inhibition higher than 70%, invo...

Insights for the design of protein lysine methyltransferase G9a inhibitors.

The epigenetic control of gene expression could be affected by addition and/or removal of post-translational modifications such as phosphorylation, acetylation and methylation of histone proteins, as well as methylation of DNA (5-methylation on cytosines). Misregulation of these modifications is associated with altered gene expression, resulting in various disease conditions. G9a belongs to the protein lysine methyltransferases that specifically methylates the K9 residue of histone H3, leading to suppressio...

Analysis of 8q24.21 miRNA cluster expression and copy number variation in gastric cancer.

 To analyze gene expression and copy number of five miRNAs (, , , and ) localized in this chromosome region in gastric cancer (GC).  65 paired neoplastic and non-neoplastic specimens collected from GC patients and 20 non-neoplastic gastric tissues from cancer-free individuals were included in this study. The expression levels of the five miRNAs were accessed by real time qPCR and were correlated.  , , and were upregulated in approximately 50% of GC tumors in relation to those of adjacent non-neoplasti...

Rational modulator design by exploitation of protein-protein complex structures.

The horizon of drug discovery is currently expanding to target and modulate protein-protein interactions (PPIs) in globular proteins and intrinsically disordered proteins that are involved in various diseases. To either interrupt or stabilize PPIs, the 3D structure of target protein-protein (or protein-peptide) complexes can be exploited to rationally design PPI modulators (inhibitors or stabilizers) through structure-based molecular design. In this review, we present an overview of experimental and computa...

Indole-3-glyoxyl tyrosine: synthesis and antimalarial activity against Plasmodium falciparum.

More than 40% of the world's population, across 105 countries, live in malaria endemic areas. It is estimated that about 500 million cases of malaria and half a million deaths occur per year.

State of the art of Smo antagonists for cancer therapy: advances in the target receptor and new ligand structures.

Since the Hedgehog signaling pathway has been associated with cancer, it has emerged as a therapeutic target for cancer therapy. The main target among the key Hedgehog proteins is the GPCR-like Smo receptor. Therefore, some Smo antagonists that have entered clinical trials, including the US FDA-approved drugs vismodegib and sonidegib, to treat basal cell carcinoma and medulloblastoma. However, early resistance of these drugs has spawned the need to understand the molecular bases of this phenomena. We theref...

Developing RNA aptamers for potential treatment of neurological diseases.

AMPA receptor antagonists are drug candidates for potential treatment of a number of CNS diseases that involve excessive receptor activation. To date, small-molecule compounds are the dominating drug candidates in the field. However, lower potency, cross activity and poor water solubility are generally associated with these compounds. Here we show the potential of RNA-based antagonists or RNA aptamers as drug candidates and some strategies to discover these aptamers from a random sequence library (∼10 seq...

Small molecules as central nervous system therapeutics: old challenges, new directions, and a philosophic divide.

Photoinactivation of ESKAPE pathogens: overview of novel therapeutic strategy.

The emergence of antimicrobial drug resistance requires development of alternative therapeutic options. Multidrug-resistant strains of Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa and Enterobacter spp. are still the most commonly identified antimicrobial-resistant pathogens. These microorganisms are part of the so-called 'ESKAPE' pathogens to emphasize that they currently cause the majority of hospital acquired infections and effectively 'es...

High-throughput hydrogen bond strength calculation and its applications in optimizing drug ADME properties.

Modifying the molecule's intrinsic hydrogen bond strength (HBS) is a useful approach in optimizing its permeability and P-glycoprotein (P-gp) efflux. Quantum mechanics (QM) based computation has been utilized to estimate the molecular intrinsic HBS. Despite its usefulness, the computation is time consuming for a large set of molecules.


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