Current Medicinal Chemistry (CURR MED CHEM )

Publisher: Bentham Science Publishers

Description

Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each bi-weekly issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

  • Impact factor
    4.07
  • 5-year impact
    4.47
  • Cited half-life
    5.50
  • Immediacy index
    0.63
  • Eigenfactor
    0.03
  • Article influence
    1.19
  • Website
    Current Medicinal Chemistry website
  • Other titles
    Current medicinal chemistry (Online)
  • ISSN
    1875-533X
  • OCLC
    55201153
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Bentham Science Publishers

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • 12 months (unless federal, government, funding agencies or local policy mandates for the author's institute a different policy on self-archiving)
  • Conditions
    • On authors personal or authors institutions server
    • Published source must be acknowledged
    • Must link to journal home page
    • Publisher's version/PDF cannot be used
    • Articles in all journals can be made Open Access on payment of additional charge
  • Classification
    ​ yellow

Publications in this journal

  • [show abstract] [hide abstract]
    ABSTRACT: Human Forkhead-Box Class O (FoxO) transcription factors, activated in response to a wide range of external stimuli, like growth factors, insulin, nutrient levels and oxidative stress, are able to control several specific gene-expression programs. Besides their clear implication in metabolic processes, they appear to play a relevant role in tumour suppression by upregulation of genes involved in cell cycle arrest or apoptosis. Recent research efforts provide new insights into the molecular modulation of FoxO in liver cancer and disclose potential opportunities for developing new antitumor drugs. Through an intricate regulatory model, achieved via several post-translational modifications, including phosphorylation, acetylation, and ubiquitination, which control their subcellular localization and DNA binding activity, FoxO factors act as tumour suppressors. Low levels of FoxOs are associated with poor prognosis in cancer patients, and seem to confer chemotherapy resistance. Within FoxO members, FoxO3a appears to present anti-tumour properties in hepatocellular carcinoma, inducing the expression of pro-apoptotic genes, or interfering with signaling cascades commonly altered in this disease such as Wnt/β-catenin, PI3K/AKT/mTOR or MAPKs pathways. Here, we describe the main mechanisms of FoxO proteins regulation, and their cross link with altered pathways in liver cancer. Moreover, based on the current knowledge of FoxO modulation, emphasis is placed on the development of novel agents which specifically activate FoxO family members and could be useful in the treatment of hepatocarcinoma.
    Current Medicinal Chemistry 04/2014; 21(10):1231-1240.
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    ABSTRACT: Synthesis and research of pharmacological properties of polyfunctional "hybrid" compounds containing fragments of nitroxyl radicals (NR) in a molecule (spin-labeled conjugates) is a rapidly developing area of medicinal chemistry. Many examples of various classes of natural compounds have shown that the introduction of nitroxyl fragment into a molecule leads to either strengthening of biological activity or its modification, decrease of general toxicity, or increase of selective cytotoxicity. The review of the published data on spin-labeled biologically active natural compounds has revealed that various classes of natural compounds, such as anthracycline antibiotics, lignans, triterpene acids, chromanes, flavonoids, stilbenoids, alkaloids, amino acids, etc. are used for obtaining conjugates with nitroxyl radicals. Some spin-labeled derivatives of natural compounds are used for the treatment and prevention of the most dangerous diseases. Conjugates of nitroxyl radicals with "molecular compasses" (e.g. folic acid, fragments of gramicidin, heparin) may well serve as drug delivery systems to pathological areas of a body for diagnostics and treatment of diseases. We have summarized the results of the last decade on the synthesis and study of biological activity of conjugates with nitroxyl radicals.
    Current Medicinal Chemistry 03/2014;
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    ABSTRACT: The use of the cannabis plant for various medical indications by cancer patients has been rising significantly in the past few years in several European countries, the US and Israel. The increase in use comes from public demand for the most part, and not due to a scientific basis. Cannabis chemistry is complex, and the isolation and extraction of the active ingredient remain difficult. The active agent in cannabis is unique among psychoactive plant materials, as it contains no nitrogen and, thus, is not an alkaloid. Alongside inconclusive evidence of increased risks of lung and head and neck cancers from prolonged smoking of the plant produce, laboratory evidence of the anti-cancer effects of plant components exists, but with no clinical research in this direction. The beneficial effects of treatment with the plant, or treatment with medicine produced from its components, are related to symptoms of the disease: pain, nausea and vomiting, loss of appetite and weight loss. The clinical evidence of the efficacy of cannabis for these indications is only partial. However, recent scientific data from studies with THC and cannabidiol combinations report the first clinical indication of cancer-related pain relief. The difficulties of performing research into products that are not medicinal, such as cannabis, have not allowed a true study of the cannabis plant extract although, from the public point of view, such studies are greatly desirable.
    Current Medicinal Chemistry 03/2014;
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    ABSTRACT: The extensively investigated serine/threonine kinase, B-RAF, is a member of the RAS/RAF/MEK/ERK pathway. It plays important role in the regulation of cell growth, differentiation and survival. The mutation of B-RAF occurs frequently in melanomas and colon tumors; therefore, it is considered as an outstanding therapeutic target. In recent years a great number of B-RAF inhibitors have been reported and this number is expected to increase. The aim of our work was to compare the structures and binding mode of the published B-RAF inhibitors, and then to apply the correlations found for the explanation of our experimental results. In the first part of this paper we describe the main pharmacophore features of the co-crysallized B-RAF inhibitors published in the literature, focusing on the binding modes and common structural elements. In the second part we present and characterize our recently developed B-RAF inhibitor family by application of in silico methods and in vitro kinetic profiling. The inhibitory activity of these compounds was determined in biochemical kinase- and cell-based assays. The docking and assay results support our conclusion that the presented compound family belongs to the type 1 ½ subgroup, they inhibit B-RAF and B-RAF(V600E) mutant in a sub-micromolar range and most of them show selectivity towards B-RAF(V600E) mutant expressing cell lines with equal or even better IC50 values than sorafenib.
    Current Medicinal Chemistry 03/2014;
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    ABSTRACT: The emergence of antibiotic resistance in microbial strains is representing one of the major threats to public health worldwide, due to the decreased or total cancelling of the available antibiotics effectiveness, correlated with the slow development of novel antibiotics. Due to their excellent biodegradability and biocompatibility, the synthetic polymers could find a lot of biomedical applications, such as the development of biomaterials with optimized properties and of drug delivery systems. This review is focusing on the applications of synthetic, biodegradable polymers for the improvement of antiinfective therapeutic and prophylactic agents (i.e., antimicrobial and anti-inflammatory agents and vaccines) activity, as well as for the design of biomaterials with increased biocompatibility and resistance to microbial colonization.
    Current Medicinal Chemistry 03/2014;
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    ABSTRACT: In multi-target drug design (MTD) medicinal chemistry aims to integrate multiple pharmacophores into a single drug molecule in order to make it active on several molecular biological mechanisms simultaneously. Given the fact that most diseases are multifactorial in nature, MTD is being pursued with increasing intensity, which has resulted in improved outcomes in disease models and several compounds have entered clinical trials. In a wide range of examples we illustrate how various functionalities have been combined within single structures and how this has affected their (pre)clinical outcome. This review describes the successful application of MTD for disorders such as neurodegenerative, cardiovascular, diabetes, metabolic and inflammatory diseases, especially focusing on the field of atherosclerosis where multi-target strategies are a promising alternative to the classical "one target-one drug" design approach.
    Current Medicinal Chemistry 03/2014;
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    ABSTRACT: Cholesterol is one of the most important molecules in cell physiology because of its involvement in several biological processes: for instance, it determines both physical and biochemical properties of cell membranes and proteins. Disruption to cholesterol homeostasis leads to coronary heart disease, atherosclerosis and metabolic syndrome. Strong evidence suggests that cholesterol also has a crucial role in the brain as various neurological and neurodegenerative disorders, including Alzheimer's, Huntington's and Parkinson diseases are associated with disruptions to cholesterol homeostasis. Here, we summarize the current knowledge about the role cholesterol plays at synaptic junctions and the pathological consequences caused by disruptions in the homeostatic maintenance of this compound.
    Current Medicinal Chemistry 03/2014;
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    ABSTRACT: Similarly to a series of chronic diseases, essential arterial hypertension (HTN) may be manifested during childhood as a blood pressure (BP) reading which repeatedly rises above the 95th percentile of population-specific standards. Since BP tends to track along the same percentiles throughout life, children with higher BPs are more likely to become hypertensive adults. When healthy measures aimed at reducing BP (i.e. body weight reduction, aerobic physical exercise, low sodium intake) have failed, pharmacological treatment is usually required. This paper aims to undertake a review of antihypertensive pharmacological therapy in children, examining the drugs used in chronic treatment as well as those administered to treat hypertensive crisis (i.e. a BP major than 99th percentile of paediatric normograms). Moreover, several important differences registered in the therapeutic approach to paediatric HTN between US and European Guidelines will be underlined.
    Current Medicinal Chemistry 03/2014;
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    ABSTRACT: During the last decades, the introduction of new, more efficient drugs, has significantly improved the heart failure (HF) therapy of adults. Therapeutic focus has shifted from simple hemodynamic manipulation to include neurohumoral modulation as a consequence of the better understanding of mechanisms of HF formation, in particular at the cellular level. The aetiologies of HF in children are remarkably different and more varied than in the adult population. Cardiac failure is usually caused by congenital heart disease and cardiomyopathy in children, whereas in adults, coronary artery disease, hypertension and myocardial infarction are the most common causes. Despite this fact, pharmacotherapy of children is based on the same drugs, usually extrapolated from adult HF regimens. A recently published study in children treated with the drugs known to be efficient in adult HF therapy, provides encouragement that the outcomes might be similarly beneficial. On the other hand, some reports outline that children with HF, especially patients with systemic right ventricles or single ventricle physiology, require specific drug guidelines. A general characteristic of HF pharmacotherapy in children is the lack of paediatrically designed drugs. Drugs currently used in the treatment of HF in paediatric patients are designed for adults, and their efficacy, safety and quality have generally not been confirmed by clinical studies of children. Aside from this, availability of commercial paediatric drug formulations labelled for treatment of HF in children significantly influences the quality and efficacy of therapy.
    Current Medicinal Chemistry 03/2014;
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    ABSTRACT: Protein-protein interactions are critical for cellular functioning, and their deregulation is involved in several diseases. Targeting these protein interacting domains could be a promising approach in drug designing. One such domain, the PDZ domain is encoded by several proteins of the nervous system in particular at the postsynaptic density site of neurons where they contribute, to signal transduction pathways and neurotransmission. Since PDZ domains have well-defined binding sites, often corresponding to short amino acid motifs at the C-termini of target partner proteins, they provide promising targets for drug discovery. Viruses are art master in manipulating the signaling machinery of the cell they infect. Some of them such as rabies virus which promotes neuron survival by disrupting peculiar PDZ complexes can serve as a source of inspiration for the design of new neuroprotective drugs. This review highlights PDZ-mediated protein interactions in nervous system and their therapeutic potential.
    Current Medicinal Chemistry 03/2014;
  • Current Medicinal Chemistry 03/2014;
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    ABSTRACT: Due to the great prevalence of persistent and recurrent implanted device associated-infections novel and alternative therapeutic approaches are intensely investigated. For reducing complications and antibiotic resistance development, one major strategy is using natural or synthetic modulators for targeting microbial molecular pathways which are not related with cell multiplication and death, as Quorum Sensing, virulence and biofilm formation. The purpose of this review paper is to discuss the most recent in vitro approaches investigating the efficiency of some novel antimicrobial products and the nano-technologic progress performed in order to increase their effect and stability.
    Current Medicinal Chemistry 03/2014;
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    ABSTRACT: In the last decade, it became clear that bile acids, in addition to their role in intestinal absorption of lipids and fat-soluble vitamins, are major regulators of metabolism. They activate signal transduction pathways through binding to the specific bile acid receptors TGR5 and FXR. Indirectly, bile acids influence metabolism via modification of the gut microbiota ecosystem. The relation between bile acid metabolism and gut microbiota composition is very complex., whereas gut microbiota modulates bile acid structure, creating a complex bile acid pool consisting of a mixture of differentially structured species, bile acids alter gut microbiota, by disturbing bacterial membrane integrity. In addition, to the effects on glucose and energy homeostasis, recent literature ascribed a role for bile acid signaling in control of inflammation and regulation of the nervous system.In this review, we discuss a selection of recent published studies describing the effects of intestinal bile acid signaling on health and disease.
    Current Medicinal Chemistry 03/2014;
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    ABSTRACT: The present review is intended to bring together the main advances in the field of nanostructured biomaterials with antimicrobial properties. It is generally accepted that the discovery of antibiotics was of great importance but, nowadays new antimicrobial agents are needed and/or their better administration routes. The limitation of the use of antibiotics is essential because of the following reasons: the excessive use of antibiotics leads to the development of antibiotic resistant microorganisms; there are some alternatives for many types of infections, many of these alternatives being less toxic and do not lead to antibiotic similar resistance. In compliance with the above presented, the use of antibiotic is recommended to be eliminated (when alternatives are available) or to be reduced by using combined therapy when possible or to administrate these drugs through targeted or loco-regional drug delivery systems.
    Current Medicinal Chemistry 03/2014;
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    ABSTRACT: Low levels of high-density lipoprotein cholesterol (HDL-C) have been associated with increased cardiovascular (CV) risk. These beneficial effects of HDL can be, at least partly, attributed to its anti-inflammatory, antithrombotic, anti-oxidant and endothelial-protective properties. However, the results of some clinical trials aiming at raising HDL-C levels are conflicting in terms of CV protection suggesting that alterations in HDL quality (and not only quantity) are involved in the atherosclerotic process. In this context, inflammation, oxidation, infection, hyperglycemia and activated platelets may modify HDL components, thus transforming HDL to a dysfunctional molecule with pro-atherogenic properties. Furthermore, some recent trials with HDL-raising drugs, such as niacin and torcetrapib, reported a lack of benefit in terms of vascular risk as well as adverse events including cancer and infections. In this narrative review, the findings of recent HDL clinical studies in relation to CV events as well as the associations of HDL with cancer and infections are discussed. The possible pathogenic mechanisms of these associations are also considered. The clinical implications of HDL function in treating patients at high CV risk remains to be established in future trials.
    Current Medicinal Chemistry 03/2014;
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    ABSTRACT: The electrophoretic separation of lipoproteins on polyacrylamide gels enables the quantification of non-atherogenic and atherogenic plasma lipoproteins including small dense low density lipoprotein (sdLDL) particles, which represent the atherogenic lipoprotein subpopulations in plasma. This methodology could help distinguish between non-atherogenic hyperlipidemia, normolipidemia with an atherogenic lipoprotein profile, non-atherogenic normolipidemia, and atherogenic hyperlipidemia. According to our pilot research of a normolipidemic population, the atherogenic lipoprotein profile might be present in about 6% of normolipidemic young healthy individuals. Therefore, if confirmed by other studies, it will be necessary to consider a different diagnostic approach and risk stratification for patients with atherogenic normolipidemia (as well as non-atherogenic hypercholesterolemia).
    Current Medicinal Chemistry 03/2014;
  • Current Medicinal Chemistry 03/2014;
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    ABSTRACT: The increasing morbidity and mortality of infectious diseases is an increasing concern. Despite the continuousdevelopment and synthesis of new antimicrobial drugs, microbial pathogens are exhibiting increased multi-drug resistance. Nanomaterials display unique and well-defined physical and chemical properties including a very high surface area to volume ratio, and new approaches for antimicrobial therapies have attempted to combine nanomaterials and current antimicrobial drugs. Magnetic nanoparticles (MNPs) are characterized by biocompatibility, biodegradation, and safety for human ingestion. Iron oxide nanoparticles have been approved for human use by the US Food and Drug Administration (FDA).For biomedicine applications, MNPs require surface modification to become water-soluble and be stable enough to resist the effects of proteins and salts in the physiological environment.MNPs can combine various substrata, such as biomolecules and nanomaterialsto generatenew antimicrobial agents which combine antibacterial, antiviral, and antifungal properties.This can be accomplished through a series of surface modification methods. Because MNPs have unique superparamagnetic characteristics, they can be controlled and recycled by an external magnetic field.In addition, the antimicrobial activity of MNPs-based nanocomposites is superior to that of metallic nanoparticles. This paper reviews the recent literature on the use of MNP-based nanomaterials in antimicrobial applications in biomedicine.Antimicrobial applications mainly focus on inhibiting and killing bacteria and fungiand viruses inactivation. The synthesis, surface modification, and characteristics related to MNPs will also be briefly addressed.
    Current Medicinal Chemistry 03/2014;
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    ABSTRACT: The primary objective of this review is to verify if there are differences in the diagnostic and therapeutic strategies in cases of PDA employed in different NICUs that might help explain the different percentages of duct closure, surgical ligation and outcome in these vulnerable patients. The secondary objective is to document if the selection of a specific NSAID and/or the way of administration are based on factors such as costs and local availability of drugs, as well as influenced by clinical and haemodynamic parameters, potential risks, local experience and the existing literature. Data Sources were MEDLINE, EMBASE, Cochrane Library and analysis of the most important papers were performed. We examined a total of 89 trials including 15,657 neonates (with gestational ages between 22 and 35 weeks and study weights between 380 and 2500 g), due to the lack of homogeneity of case studies it was not possible to standardize for gestational age and weight. To simplify, the studies we considered were subdivided into 5 groups corresponding to 5 tables: 1- INDO-prophylaxis (15 trials); 2- IBU-prophylaxis (11 trials); 3- INDO-therapy (18 trials); 4- IBU-therapy (16 trials); 5- IBU vs INDO therapy (29 trials). Each table reports the journal, the author and year, the type of study, the number of neonates enrolled, the drugs used, management after failure of the first cycle, percentage of duct closure and adverse effects. Treatment with indometacin is prescribed prevalently in the United States and Canada. According to the data collected, prolonged treatment and administration of high doses would appear to be more effective. The early administration of indometacin has been associated with gastrointestinal bleeding, renal insufficiency, altered cerebral self-regulation and, especially when administered together with postnatal steroids, it has been correlated with isolated intestinal perforation. Ibuprofen treatment is preferred in Europe but it may be associated with nephrotoxicity and an increase in BDP and ROP, although less frequently compared to indometacin. Indometacin is associated with major nephrotoxicity, as well as with a higher incidence of NEC, intestinal perforations and a reduced cerebral blood flow. Despite this, the administration of ibuprofen does not appear to be without short- and long-term renal adverse effects.
    Current Medicinal Chemistry 03/2014;
  • Current Medicinal Chemistry 03/2014;

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