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 3.72

  • Hide impact factor history
     
    Impact factor
  • 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: A large amount of pesticides are being used now-a-days in crop protection which has resulted in buildup of such harmful compounds in the environment, proving a menace to humans, animal life as well as to soil microbes. Residues of these pesticides have been reported in soil, water and foods. Carbendazim and sulfosulfuron are among the most widely used pesticides for treating fungal diseases and unwanted herbs in crops respectively. Carbendazim is a benzimidazole fungicide which can harm liver as well as the endocrine system and suspected to have mutagenic and tumorigenic effects. On similar lines sulfosulfuron, a sulfonylurea herbicide may result in the development of resistant herbs displaying its carry-over effects to the next crop cultivated. These pesticides possess large half-lives and thus remain persistent in the environment which may lead to harmful consequences in near future. Besides chemical and photo-catalytic degradation of pesticides, microbial degradation has now been evolved as a much effective and safer way to eradicate these harmful compounds from the environment. However a limited literature is available on the microbial degradation of such compounds. The present review emphasizes mainly upon the chemical properties of Carbendazim and Sulfosulfuron, detection of their residues, harmful effects and insights into their degradation studies. Further, the use of efficient microbes for remediation of pesticides from the environment has been discussed.
    Current Medicinal Chemistry 01/2015;
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    ABSTRACT: Tuberculosis continues to be a deadly infectious disease, mainly due to the existence of persistent bacterial populations that survive drug treatment and obstruct complete eradication of infection. The enzymes GlgE and GlgB, which are involved in the glycan pathway, have recently been identified as promising drug targets for combating persistent bacillus strains. In the glycan pathway, enzymes GlgE, GlgA, and Tre-xyz produce linear α-glucans, which are then converted to essential branched α-glucan by GlgB. This α-glucan is a vital cell-wall and storage polysaccharide, critical for Mtb virulence and persistence. We highlight recent insights into the significance of both GlgE and GlgB in the glycan pathway and also discuss drug strategies for tuberculosis such as polypharmcological targeting of GlgB and GlgE. Small molecule-based modulation of GlgB and GlgE to boost the design and development of novel and improved drugs for more selective and efficient targeting of tuberculosis are also discussed.
    Current Medicinal Chemistry 08/2014;
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    ABSTRACT: Apoptosis is a highly programmed cell death strictly connected to the pathogenesis of many human diseases, including neoplastic, neurodegenerative or cardiovascular diseases. Mitochondria play a key role in the apoptotic process; their damage activates a series of events which provoke the release of cytochrome c and other pro-apoptotic factors from the mitochondrial intermembrane space, and culminate in cell death. This review provides an overview of the key role played by mitochondria in the activation of the apoptotic process. In particular, the interest is focused on the role played by cardiolipin, a phospholipid deeply involved in the first steps of the process culminating in cell apoptosis. Mitochondrial phospholipids are involved in several cellular functions, such as cell respiration, apoptosis, and autophagy. Therefore, any alteration in the production of phospholipids or in their structural properties causes deep effects on the cell behavior and induces the arising of different pathologies. The present review summarizes the most recent advances in the study of the role that CL, a phospholipid possessing a unique structure, plays in mitochondrial activity, in apoptosis, and in the onset of human diseases.
    Current Medicinal Chemistry 04/2014;
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    ABSTRACT: Numerous basic-helix-loop-helix (bHLH) transcription factors(TF) have been found to play important roles in tumor growth and progression.Elucidation of the common features of these TFs can pave the road to possible therapeutic intervention. The existing studies of possible inhibition of these TFs are concentrated on the development of peptides or small molecules that inhibit the dimerization of these TFs or prevent their DNA binding. The bHLH TFs have striking similarity in many functionally important regions, such as the helical regions of TFs that interact with each other during dimerization and have complementary sets of residues on both sides of a dimer. These are hydrophobic residues along with anionic and cationic residues with complementary charges.Such complementarity also exists in other contact regions of the bHLH TFs. They also have a very specific set of positivelycharged residues on the surface,which would contact DNA. Such specificity defines a common concept foran in-silicodesign of bHLH TFs inhibitors for a number of existing and important cancer relatedTFs.
    Current Medicinal Chemistry 04/2014;
  • Current Medicinal Chemistry 04/2014;
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    ABSTRACT: Ovarian cancer is an extremely aggressive disease in which the vast majority of patients face a very poor prognosis. Although most patients initially respond to current chemotherapeutic regimens that include a combination of platinum-based therapy (cisplatin/carboplatin) and paclitaxel, the vast majority of them quickly relapse and develop increased resistance to available treatments. Thus, intrinsic and acquired chemotherapy resistance is a major obstacle in the treatment of ovarian cancer patients. Consequently, the priorities for basic and translational ovarian cancer research need to include the identification of novel therapies directed against key molecular targets and signaling pathways in platinum resistant disease. At the same time, we need to develop novel systems for drug delivery aimed at increasing the efficacy and reducing the toxicity of platinum-based treatments. Improving the current responses to platinum chemotherapy is critical not only for achieving a better outcome clinically, including a longer survival, but also for allowing patients to have a better quality of life while in treatment.
    Current Medicinal Chemistry 04/2014;
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    ABSTRACT: Epidemiological surveys and molecular studies have indicated that infection of human papillomavirus (HPV)itself is necessary butinsufficient for completing transformation of the human epithelial cells in vivo to lead to differentcancers. Mounting evidence exists that HPV E6/E7 oncoproteins exactly alter thecellular and molecular events in their transformed cells to induce cancers through a phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway.ThePI3K/Akt/mTOR signalingpathwayis,nonetheless, of central importance, which tightly modulates many cellular events that occur in cells to lead them to be cancerous under the action of oncogenic factors. The cancinogenicrolesof the PI3K/Akt/mTOR signalings in HPV-induced cancers are generally regulated by differentupstream signaling molecules such as upstream receptor tyrosine kinases. In this article, we review the regulatory roles of four major upstream signaling molecules (growth factor receptor, notch receptor, Ras and PI3KCAgenes) in PI3K/Akt/mTOR pathway to result in mutation or amplification of the major elements in the pathway to confer oncogenicity in HPV-immortalized epithelial cells and various transformed phenotypes.
    Current Medicinal Chemistry 04/2014;
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    ABSTRACT: Modern anti-cancer treatment involves targeted therapy that aims at inactivating particular oncoproteins or signaling pathways in a cancer-type-specific manner. A number of potent targeted therapies affecting oncogenic kinases or receptor tyrosine kinases have revolutionized anticancer treatment. These drugs inactivate signaling pathways that cancer cells depend on and therefore inhibit their proliferation and survival. Molecular chaperones of the Hsp90 family (heat shock protein 90) support the integrity, folding and function of many proteins involved in proliferation, survival, DNA damage and repair. Hsp90 proteins are thus required to maintain activity of a large variety of oncogenic proteins, including members of the JAK/STAT and the PI3K pathways. Accordingly cancer cells rely on Hsp90 proteins and their expression is often elevated in malignant cells. In line with this, inhibitors of Hsp90 (Hsp90-Is) have demonstrated potentanti-tumor activity in preclinical studies. While Hsp90-Is can be considered as targeted therapy, their broad effects on multiple signaling pathways make it difficult to predict the therapeutic outcome. Multiple myeloma (MM) is one of the tumor types with elevated Hsp90 levels. Hsp90-Is demonstrated promising activity in preclinical studies of MM and in several clinical trials. However, large variability in response questioned the use of Hsp90-Is as single drugs in the treatment of myeloma. A critical factor in targeted therapies, including Hsp90-Is, is identification of susceptible subgroups of patients. Predictive biomarkers in each particular tumor type are important in order to use anticancer drugs in a rational way. Interestingly, levels of Hsp90 expression has not proven to be decisive for treatment response and hence stratification of myeloma patients. Others and wehave recently found that MM cells with an IL-6-activated JAK/STAT3 pathway are particularly sensitive to Hsp90-Is. In this review we will discuss these findings, both in terms of molecular mechanisms and applications for selection of MM patients amenable to Hsp90-I treatment in an individually targeted treatment strategy.
    Current Medicinal Chemistry 04/2014;
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    ABSTRACT: Drug resistance is one of the major reasons for the failure of cancer therapies. Although our understanding of resistance to targeted cancer drugs remains incomplete, new and more creative approaches are being exploited to intercept this phenomenon. Considerable advances have been made in our understanding that cancer drug resistance can be caused by alterations of drug efflux, increases in drug metabolism, mutations of drug targets, alterations in DNA repair and cell cycle, changes in cell apoptosis and autophagy, induction of epithelial-mesenchymal transition (EMT) and the generation of cancer stem cells (CSCs). Furthermore, intracellular signalling pathways have been shown to play key physiological roles and the abnormal activation of signalling pathways may be correlated with drug resistance. Recently, noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have emerged as important regulators of gene expression and alternative splicing, which provides cells with yet another mode to greatly increase regulatory complexity and fine-tune their transcriptome and can rapidly adjust their proteome in response to stimuli. Consequently, a wide variety of biological functions have been shown to depend on the coordinated interactions between noncoding RNAs and cellular signalling networks to achieve a concerted desired physiological outcome, whereas mutations and dysregulation of ncRNAs have been linked to diverse human diseases, including cancer drug resistance. In this review, we will discuss recent findings on the multiple molecular roles of regulatory ncRNAs on the signalling pathways involved in cancer drug resistance and the therapeutic potential of reverse drug resistance.
    Current Medicinal Chemistry 04/2014;
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    ABSTRACT: High density lipoprotein (HDL) has two important roles: a) it modulates inflammation, and, b) it promotes reverse cholesterol transport. HDL‑cholesterol levels are inversely correlated with the risk of cardiovascular events. The main component of HDL, apolipoprotein A‑I (apo A‑I), is largely responsible for reverse cholesterol transport through the macrophage ATP‑binding cassette transporter ABCA1. Apo A‑I can be damaged by oxidative mechanisms, which render the protein less able to promote cholesterol efflux. HDL also contains a number of other proteins that are affected by the oxidative environment of the acute‑phase response. Modification of the protein components of HDL can convert it from an anti‑inflammatory to a pro inflammatory and dysfunctional particle. Small peptides that mimic some of the properties of apo A‑I have been shown in preclinical models to improve HDL function and reduce atherosclerosis without altering HDL‑cholesterol levels. Endothelium is the interface between the blood and the extra vascular environment regulating the traffic of vital molecules between the blood and tissues. Oxidative stress and excess levels of reactive oxygen species disrupts the normal function of endothelium. HDL and other antioxidant/anti-inflammatory systems prevent endothelial dysfunction and maintain the critical balance needed for normal vascular function.
    Current Medicinal Chemistry 04/2014;
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    ABSTRACT: Chronic kidney disease (CKD) is an emerging health hazard, connected to very high cardiovascular mortality due to accelerated atherosclerosis. Increased cardiovascular risk cannot be explained only by traditional risk factors. Patients with renal dysfunction have significant disturbances in lipoprotein metabolism and HDL in these patients becomes dysfunctional. It has been documented that in patients with CKD are lower plasma level of HDL cholesterol and reduced ability of HDL to bind to ABCA1 are seen, which results in slowing down the reverse cholesterol transport and disturbances in HDL maturation due to decreased lecithin cholesterol ester transfer protein. Studies demonstrated that HDL of CKD patients loses its vasoprotective, antioxidative and anti-inflammatory properties and turns into a noxious particle which promotes endothelial dysfunction via stimulating superoxide production and limiting NO bioavailability. Alterations of HDL at the 'molecular and functional level', are also seen in renal transplant recipients even in those with excellent graft function.
    Current Medicinal Chemistry 04/2014;
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    ABSTRACT: For more than 20 years there has been increasing interest in the development of novel therapies to raise levels of high-density lipoprotein cholesterol (HDL-C). However, well publicized failures of recent clinical trials of agents that raise HDL-C levels have stimulated considerable controversy with regard to the potential clinical utility of this therapeutic target. A number of classes of agents are currently under investigation with variable effects on HDL quantity and quality. These will be reviewed.
    Current Medicinal Chemistry 04/2014;
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    ABSTRACT: Activation of hypoxia-inducible factor 1 (HIF-1) signaling is observed in a broad range of human cancers due to tumor hypoxia and epigenetic mechanisms. HIF-1 activation leads to the transcription of a plethora of target genes that promote physiological changes associated with therapeutic resistance, including the inhibition of apoptosis and senescence and the activation of drug efflux and cellular metabolism. As a result, targeting HIF-1 represents an attractive strategy to enhance the efficacy of current therapies as well as reduce resistance to chemotherapy in tumors. Approaches to inhibit HIF-1 signaling have primarily focused on reducing HIF-1α protein levels, by inducing its degradation or inhibiting its transcription, inhibiting HIF-1-mediated transcription, or disrupting the formation of the HIF-1 transcription factor complex. To date, multiple preclinical and clinical agents have been identified that effectively inhibit HIF-1 activity through various mechanisms, likely accounting for a portion of their anti-tumor efficacy. This review aims to provide an overview of our current understanding of the role of HIF-1 in therapeutic resistance and discuss the ongoing effort to develop HIF-1 inhibitors as an anti-cancer strategy.
    Current Medicinal Chemistry 04/2014;
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    ABSTRACT: The phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR pathway is one of the most frequently activated signaling pathways in prostate cancer cells, and loss of the tumor suppressor PTEN and amplification of PIK3CA are the two most commonly detected mechanisms for the activation of these pathways. Aberrant activation of PI3K/Akt/mTOR has been implicated not only in the survival and metastasis of prostate cancer cells but also in the development of drug resistance. As such, selective inactivation of this pathway may provide opportunities to attack prostate cancer from all fronts. However, while preclinical studies examining specific inhibitors of PI3K or mTOR have yielded promising results, the evidence from clinical trials is less convincing. Emerging evidence from the analyses of some solid tumors suggests that a class of dual PI3K/mTOR inhibitors, which bind to and inactivate both PI3K and mTOR, may achieve better anti-cancer outcomes. In this review, we will summarize the mechanisms of action of these inhibitors, their effectiveness when used alone or in combination with other chemotherapeutic compounds, and their potential to serve as the next generation therapies for prostate cancer patients, particularly those who are resistant to the frontline chemotherapeutic drugs.
    Current Medicinal Chemistry 04/2014;
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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;