Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents

Publisher: Bentham Science Publishers

Description

Current Medicinal Chemistry-Anti-Inflammatory & Anti-Allergy Agents aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new Anti-Inflammatory & Anti-Allergy Agents. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in Anti-Inflammatory & Anti-Allergy medicinal chemistry. Current Medicinal Chemistry-Anti-Inflammatory & Anti-Allergy Agents 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 in Anti-Inflammatory & Anti-Allergy Agents drug discovery. Discontinued. Continued by Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (1871-5230).

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  • Website
    Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents website
  • Other titles
    Anti-inflammatory & anti-allergy agents, Anti-inflammatory and anti-allergy agents
  • ISSN
    1568-0142
  • OCLC
    52852761
  • Material type
    Periodical, Internet resource
  • Document type
    Journal / Magazine / Newspaper, Internet Resource

Publisher details

Bentham Science Publishers

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    • 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)
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    • On authors personal or authors institutions server
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    • 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

  • Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents 01/2012; 11(1):3751.
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    ABSTRACT: Vitamin D receptor (VDR) agonists are well-known for their capacity to control calcium metabolism and to regulate growth and differentiation of many cell types. More recently, it has become clear that VDR agonists possess exquisite immunoregulatory properties, mostly by targeting dendritic cells and T cells. These properties have been exploited in the treatment of several Th1-mediated experimental autoimmune diseases, and a considerable body of work documents their beneficial effects in inhibiting the development of type 1 diabetes (T1D), a chronic-progressive autoimmune disease leading to the destruction of insulin-producing pancreatic β cells. This review analyzes the capacity of different VDR agonists to inhibit spontaneous T1D development in the non-obese diabetic (NOD) mouse, and shows that 1α,25-(OH)2-16,23Z-diene-26,27-hexafluoro-19-nor D3 (compound 6) is the most effective analog, among those tested, in delaying and reducing disease progression. Identified mechanisms of action underlying the efficacy of this VDR agonist in inhibiting T1D development in the NOD mouse are also reviewed.
    Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents 11/2005; 4(6):645-651.
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    ABSTRACT: Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors with key metabolic roles in adipose tissue, liver and skeletal muscle. They are also expressed at significant levels in polymorphonuclear cells, monocyte/ macrophages, dendritic cells, T cells and B cells, suggesting that they may have a role in modulating the immune response. To date, evidence for such a role comes from numerous studies describing changes in gene expression within immunoregulatory cells in response to pharmacological PPAR ligands, reports of beneficial effects of PPAR agonists in auto-immune disease in rodents, and accelerated auto-immune disease in genetically modified rodents with reduced PPAR expression. Coupled with the knowledge that the PPARs may act as "lipid sensors", these data have added to the growing scientific awareness of links between nutritional status and immune function.
    Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents 11/2005; 4(6):631-635.
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    ABSTRACT: Histamine is a biogenic amine with a broad spectrum of activities in various physiological and pathological situations. Besides its well-characterised effects in allergic responses and in acute inflammation, histamine modulates the cytokine network, influencing T helper 1 and T helper 2 balance, and antibody isotype. In multiple sclerosis (MS), and its animal model of experimental autoimmune encephalomyelitis (EAE), there are several steps in the autoimmune attack against myelin of the central nervous system where histamine might play an important role. Indeed, blockade of specific histamine receptors has been proven to prevent early acute EAE by reducing encephalitogenic T helper 1 response and altering antigen presentation. A deeper understanding of the mechanisms by which histamine regulates the development and progression of EAE and MS might open new strategies for immune intervention.
    Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents 11/2005; 4(6):637-643.
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    ABSTRACT: Tumor necrosis factor receptor associated periodic syndrome (TRAPS) is a hereditary auto-inflammatory periodic fever syndrome associated with autosomal dominant ectodomain mutations in the 55kDa tumor necrosis factor receptor (TNFRSF1A). Over forty mutations in TNFRSF1A are associated with TRAPS. Plasma levels of soluble TNFRSF1A (sTNFRSF1A) are abnormally low in TRAPS patients, as is shedding of TNFRSF1A by some patients' leucocytes. It was hypothesised that a deficit in neutralisation of TNF by sTNFRSF1A in TRAPS might result in an increased sensitivity to the inflammatory effects of TNF. However, not all TRAPS-related TNFRSF1A mutations result in defective receptor shedding by leucocytes. We found that dermal fibroblasts, but not leucocytes, from TRAPS patients with C33Y mutation demonstrated reduced shedding of TNFRSF1A, and that shedding of both wild-type and mutant truncated TNFRSF1A from transfected cell lines was similar. It is unlikely that a defect in TNFRSF1A shedding fully explains the clinical features of TRAPS. We investigated the behaviour of TRAPS-related TNFRSF1A mutants compared with wildtype in transfected cell lines: the mutant forms of TNFRSF1A retained signalling functions, but showed abnormalities of intra-cellular trafficking and TNF binding suggestive of protein misfolding. The severity of the abnormalities were observed with different mutants correlated with the degree of penetrance and clinical severity. We hypothesise that aggregation and ligand-independent signalling of mutant TNFRSF1A may occur. The increased understanding of the genetic basis and pathophysiology of TRAPS has facilitated therapeutic advances in the clinical management of this condition, particularly the use of the TNF-neutralising agent etanercept.
    Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents 11/2005; 4(6):577-585.
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    ABSTRACT: Antihistamines have an important role in dermatology. In order to understand how antihistamines work, effects of histamine should be examined first. Histamine was first defined in 1920s and was shown to take part in the pathogenesis of diseases such as urticaria, anaphylaxis, asthma, and allergic rhinitis. The main goal in the treatment of urticaria and other diseases related to histamine is to keep this powerful mediator's effects under control. So many antihistamines have been presented to the market since 1942 and still, new compounds are being developed. For years, antihistamines have been categorized as first, second and third generation. In this text, a review of the action mechanism of antihistamines and the new antihistamines will be presented.
    Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents 09/2005; 4(5):465-475.
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    ABSTRACT: We found that compounds, which can selectively inhibit the activity of mammalian DNA polymerase (pol ) in vitro, show an anti-12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammatory effect in mice. Originally, we screened selective inhibitors for each of the mammalian DNA polymerases, and found two novel pol -inhibitors, phenolic compounds termed petasiphenol and curcumin (diferuloylmethane). Curcumin is known as an anti-chronic inflammatory agent and structurally quite similar to petasiphenol. The IC50 values of petasiphenol and curcumin for pol were 7.8 M and 7.0 M, respectively, and neither compound influenced any other mammalian DNA polymerases. Expectedly, petasiphenol also showed an anti-TPA-induced inflammatory effect. A relationship between the pol -inhibition and the anti-inflammatory activity is suggested. Therefore, we investigated whether other anti-inflammatory compounds such as terpeno benzoic acids, triterpene acids and epolactaene derivatives could be pol -inhibitors. Although all the compounds influenced not only several different DNA polymerase species but DNA topoisomerase II, they all most efficiently inhibited the pol -activity. These results unexpectedly suggest that there is a physiological relationship between pol l inhibition and anti-TPA-induced inflammation. This finding may provide insight into the molecular mechanism of TPAinduced inflammation, or neoplastic promotion.
    Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents 09/2005; 4(5):543-553.
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    ABSTRACT: H1 antihistamines are first line drugs in the treatment of allergic rhinitis and chronic idiopathic urticaria and widely used in children as well as in adults. Although first-generation antihistamines are effective in relieving allergic symptoms, they are not preferred because of their sedative side effects. The earliest "second generation" antihistamines, terfenadine and astemizole, non-sedating alternatives to the first generation counterparts are not commonly used due to their potential arythmogenic effects. The newer second-generation antihistamines such as loratadine, fexofenadine, mizolastine, ebastine, cetirizine, levocetirizine and desloratadine have been shown to be efficacious and well tolerated with additional anti-inflammatory effects and lacking cardiotoxic potential activity in adults. The early treatment of atopic children study, the long term clinical trial with cetirizine of infants with atopic dermatitis demonstrated that cetirizine delayed the onset of asthma in patients sensitized to grass pollen or house dust mite; and also reduced the duration and the amount of topical steroids used in the treatment of atopic dermatitis. In the Preventia I study, which was designed to evaluate the efficacy of loratadine in reducing the number of respiratory infections in young children at risk of recurrent infections, loratadine was not found to be significantly different from placebo. Both drugs were found to have a similar safety profile to that of placebo confirming their long-term use in infants and children. Pediatric formulation of desloratadine, which has favorable effect on nasal congestion, is marketed worldwide now. The effectiveness of new antihistamines in the treatment of urticaria in pediatric age group is based on extrapolation of adult studies performed in this area. Further studies with new antihistamines are needed for their evidence-based use in children with urticaria and atopic dermatitis.
    Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents 09/2005; 4(5):495-506.
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    ABSTRACT: Allergy skin tests are the best and most reliable method of diagnosing allergies. Medications may influence the interpretation of skin testing. Antihistamines interfere with prick and intradermal skin tests, while they do not suppress patch tests. Some other medications also have influence on allergy skin tests. It's important to know the suppression mechanism and the duration of the inhibitory effect of these drugs on the skin test to get correct interpretation, which would be a valuable guide in allergen identification and avoidance in treatment of allergies. Allergic diseases are common and bothering medical problems in pregnant patients. It's generally recommended to avoid all medications during pregnancy, if possible. But sometimes antihistamines are needed to be used in the treatment of allergic diseases regarding the benefit/risk ratio. In such cases, antihistamines should be carefully chosen. Considering the animal and human data available, chlorpheniramine seems to be the antihistamine to choose with the least risk.
    Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents 09/2005; 4(5):517-519.
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    ABSTRACT: Allergic rhinitis is a common disease worldwide and antihistamines remain the mainstay of pharmacotherapy for allergic rhinitis. Histamine is one of main mediators involved in the disease pathophysiology. The primary mechanism of antihistamine action is believed to be competitive antagonism of histamine receptors, specifically the H1-receptors. These receptors are present on nerve endings, smooth muscles, and glandular cells. However, H1- antagonism may not be their sole mechanism of action. Antihistamines have been used in two forms; oral and topical, in the management of allergic rhinitis. The use of the first-generation oral antihistamines (chlorpheniramine, diphenhydramine, promethazine, tripolidine, clemastine, and tripelennamine) is considerably limited by their sedative and anticholinergic effects. The secondgeneration antihistamines (acrivastine, astemizole, azelastine, cetirizine, ebastine, fexofenadine, loratadine, mizolastine, and terfenadine) are effective in reducing nasal symptoms, and have no sedative effects. However, terfenadine, astemizole and recently, loratadine, have been found to cause prolongation of the QT interval on electrocardiogram, and can increase the risk for development of potentially lethal ventricular tachyarrhythmias, or torsades de pointes. The next-generation antihistamines (fexofenadine, desloratadine, tecastemizole, and levocetirizine) are typically the structurally modified, active metabolites or isomers of second-generation antihistamines. These agents retain the non-sedating properties of second- generation antihistamines while eliminating or limiting the cardiac risks. Topical antihistamines (azelastine and levocabastine), delivered by nasal spray, avoid or minimize systemic adverse effects. They have a rapid onset of action (less than 15 min) at low drug dosage, but their action is limited to the treated organ.
    Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents 09/2005; 4(5):477-480.
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    ABSTRACT: Antihistamines are already among the most frequently used pharmaceutical compounds and with the predictable increase of the prevalence of atopic disease, even more patients are expected to use them in future. Though the common belief on their safety has existed since some decades, they, including the over the counter ones, might potentially bear serious side effects. Thus , the following article focuses on the adverse effects of antihistamines by summarizing the current data mainly on central nervous system and cardiovascular side effects. Meanwhile, less common side effects, and important issues like their use in pregnancy and lactation are also included. Updated information is provided on drug interactions and overdose situations along with their management. As a finalstep, pitfalls in choosing suitable antihistamine/ s in special circumstances to avoid adverse effects are also covered.
    Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents 09/2005; 4(5):507-515.
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    ABSTRACT: H1 antihistamines are widely used in the treatment of allergic disorders. The CNS depressant and antimuscarinic effects of the first generation compounds limited their use in allergic disorders, and the second generation compounds were developed to reduce or eliminate these effects. However, the use of the first second generation H1 antihistamines, terfenadine and astemizole, under certain circumstances, was associated with adverse cardiac effects, which were occasionally fatal and they were withdrawn from the market. This review examines the pharmacokinetics of the second generation antihistamines and the impact of the pharmacokinetic properties on their efficacy and safety, particularly with regard to their effects on the central nervous and cardiovascular systems and their potential for interactions with concomitantly administered drugs and dietary components.
    Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents 09/2005; 4(5):451-464.
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    ABSTRACT: This review focuses on the physiology of mitochondria as well as on the role of mitochondrial changes in cancer and in the immune system. After discussing the origin, structure, function and physiology of mitochondria, we focus on mitochondrial damage induced by antiviral and other drugs, reactive oxygen intermediates, physical tests like heat shock and ionizing radiation, hypoxia and hyperoxia. While discussing the effects of these noxious stimuli on mitochondria, we introduce terms such as “mitotoxicity” and “mitotoxins”. Further parts of the review focus on the role of mitochondria in programmed cell death, and mitochondrial dysfunction observed in cancer. A significant portion of the review discusses the role of mitochondrial changes during the aging of the immune system, age-related changes of mitochondrial physiology, and mitochondrial proteins as auto-antigens. Using primary biliary cirrhosis as an example, we illustrate that the autoimmune condition is perpetuated by a pathologic immune response directed towards mitochondrial antigens. Finally we raise several questions, which we believe, need to be answered in order to improve the therapy of cancer autoimmunity and genetic diseases involving mitochondria.
    Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents 07/2005; 4(4):439-448.
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    ABSTRACT: Gene vaccines against defined antigens represent a novel and promising immunization approach for cancer immunotherapy and for battling infectious diseases. Immunization with plasmid DNA is the simplest gene-based approach. In order to induce protective antitumor immunity, gene vaccines are designed to deliver one or several genes encoding tumor-associated antigens, thereby eliciting or augmenting antigen-specific immune responses. The efficacy of gene vaccines can be significantly improved through integration of advances in immunology and molecular biology. Recent evidences point out the central role of dendritic cells and show the importance of innate immune responses in the induction and enhancement of antigen-specific adaptive immune responses. Hence, manipulations that integrate both tumorassociated antigens and 'danger' signals in the vaccine design, can achieve activation of both innate and adaptive immune responses, thereby overcoming the self-tolerance towards many tumor antigens. Coadministration of genetic adjuvants and optimized prime-boost strategies enhance the efficacy of gene vaccines. In this context, strategies that target antigens of choice to dendritic cells and induce, in vivo, antitumor immune responses are discussed. This review highlights vaccine strategies based on transfer of nucleic acid sequences encoding well-defined tumor-associated antigens and genetic adjuvants to the host in vivo in order to induce successful antitumor immunity.
    Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents 07/2005; 4(4):353-365.
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    ABSTRACT: Deregulation of apoptosis resulting either in inappropriate loss or accumulation of cells is a major cause of many severe pathological conditions such as cancer, autoimmune diseases, microbial infections and degenerative disorders. Consequently, great interest has emerged in devising therapeutic strategies for intervening with cell death, either in a pro- or antiapoptotic direction. Among the different apoptosis-based drug targets, caspases, a family of intracellular cysteine proteases are most promising candidates, because they form the central core of the apoptotic machinery that coordinate cell death from various signals. Inappropriate cell death can be efficiently blocked by caspase inhibitors, whereas caspase activation or the inhibition of endogenous caspase inhibitors might be useful for the eradication of unwanted cells. Currently, numerous novel approaches are being followed employing gene therapy, antisense strategies, recombinant biologics or organic chemistry in order to target caspases or their endogenous inhibitors. Exciting proof-of-principle evidence obtained in several animal models confirms the validity of strategies targeting caspases and their enormous therapeutic potential. Although mostly in preclinical state, several therapeutics have recently progressed to clinical testing or were even approved by drug administration. This review summarizes the recent advances in the field of caspase targeting and discusses its wide-ranging opportunities for different human diseases.
    Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents 07/2005; 4(4):407-419.
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    ABSTRACT: Polymorphonuclear neutrophils (PMNs) have received less attention than other leukocyte subsets as potential mediators of antitumor effects. However, there is a growing body of evidence that PMNs are potential mediators of antitumor effects and play an important role in the antitumor response. A protein complex S100A8/A9, formed by the two low molecular weight calcium-binding proteins S100A8 and S100A9, is released from activated PMNs and has apoptosis/ cytotoxicity-inducing activity against tumor cell lines. In this review, we focus on the molecular mechanisms by which S100A8/A9 induces apoptosis. Recent studies point to a yet undefined mechanism, probably relaying on cell surface receptor( s), by which S100A8/A9 induces apoptosis in carcinoma cell lines, in addition to zinc exclusion from target cells. Although a number of putative receptors have been identified, the cell-membrane bindings site(s) involved in the apoptosis- inducing activity of S100A8/A9 remain unknown. The identification of the binding site(s) together with the elucidation of the underlying molecular mechanisms will give new insights in how the adaptive immune system is involved in cancer regression.
    Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents 07/2005; 4(4):383-391.
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    ABSTRACT: Apoptosis is a noninflammatory process used by multicellular organisms to eliminate unwanted cells. It is implemented by a family of cysteine proteases called caspases through their cleavage of cellular proteins. The upstream events leading to caspase activation are controlled at multiple levels by an extensive array of proteins, including death receptors, adapters, transcription factors and Bcl-2 family members, while acting downstream to curb caspase activity are the inhibitor of apoptosis proteins (IAPs). Since their initial discovery much has been learned about how IAPs regulate cell death and are themselves regulated. Structural studies have given us insight into how IAPs interact with and neutralise caspase activity, proteomic approaches have uncovered IAP interacting molecules, such as DIABLO/SMAC, that can antagonise IAP function, and additional modes of IAP regulation at the transcriptional and post translational level have been identified. Their potential involvement in conferring cancer cell resistance to apoptotic stimuli, e.g. chemotherapeutic drugs, has presented them as plausible targets for cancer therapy. Conversely, they may be beneficial in protecting neuronal cells from inappropriate apoptosis observed in many different neurological diseases. What follows is a discussion of the various mammalian IAPs and other BIR domain containing proteins (BIRPs), focussing on their structure, function and regulation by antagonists as well as their possible involvement in disease processes.
    Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents 07/2005; 4(4):393-406.
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    ABSTRACT: This review describes our current understanding of telomere length polymorphism and organization in breast cancer cells. The key roles of the telomeric DNA protein complexes as protectors of chromosomal ends in normal and cancer cells are under much attention in current research, and here we review some of these issues. In general the functionality of telomeres depends on a number of associated factors, like - (1) the length of the telomeric sequence at a particular chromosomal end, (2) the status of telomerase activity, (3) the telomere associated proteins, (4) the status of subtelomeric heterochromatinization, (5) or associated chromosomal instability. Specifically, in breast cancer, depending on the presence or absence of the mutations in DNA repair proteins the telomere function becomes much more fragile. Some recent studies using modern high performance three-dimensional (3D) imaging technologies indicate that many exciting aspects of this multifaceted telomere research are going to unfold further in the coming years.
    Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents 07/2005; 4(4):421-428.