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Special Issue "Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry"

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A special issue of Molecules (ISSN 1420-3049).

Deadline for manuscript submissions: closed (30 April 2013)

Special Issue Editor

Guest Editor
Prof. Dr. Arduino A. Mangoni

Department of Clinical Pharmacology, Flinders University and Flinders Medical Centre, Bedford Park, SA 5042, Australia
Website | E-Mail
Interests: arginine metabolism, nitric oxide synthesis, biological effects, ageing, cardiovascular pharmacology

Special Issue Information

Dear Colleagues,

Although anti-inflammatory agents are extensively prescribed across all age groups worldwide there are several unanswered questions about their exact mechanism of action and their potential renal and cardiovascular toxicity. These issues are largely related to 1) the validity of available methods for assessing selectivity towards the cyclooxygenase enzyme isoforms COX-1 and COX-2; 2) the exact role played by COX-1 and COX-2 in renal and vascular homeostasis in animal models and humans; and 3) the interpretation of data from pharmacoepidemiological studies and meta-analyses.
This special issue of Molecules welcomes previously unpublished manuscripts covering all aspects of pharmacology and chemistry of anti-inflammatory drugs, in particular the development of novel anti-inflammatory drugs and methods for assessing COX selectivity, pharmacodynamic effects of novel and existing anti-inflammatory drugs in animal models and humans, and the expression and role of different COX isoforms in the kidney and vasculature.

Prof. Dr. Arduino A Mangoni
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs).

Keywords

  • organic chemistry
  • drug development
  • enzyme kinetics
  • enzyme expression
  • pharmacokinetics
  • pharmacodynamics
  • cyclooxygenase
  • safety
  • renal toxicity
  • cardiovascular toxicity
  • inflammation
  • pain
  • medicinal chemistry

Published Papers (10 papers)

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Research

Jump to: Review

Open AccessArticle Molecular Docking and Fluorescence Characterization of Benzothieno[3,2-d]pyrimidin-4-one Sulphonamide Thio-Derivatives, a Novel Class of Selective Cyclooxygenase-2 Inhibitors
Molecules 2014, 19(5), 6106-6122; doi:10.3390/molecules19056106
Received: 15 January 2014 / Revised: 2 May 2014 / Accepted: 9 May 2014 / Published: 14 May 2014
Cited by 1 | PDF Full-text (1565 KB) | HTML Full-text | XML Full-text
Abstract
The aims of this study were: (i) to explore the structure-activity relationship of some new anti-inflammatory benzothieno[3,2-d]pyrimidin-4-one sulphonamide thio-derivatives 111; and (ii) to evaluate the possibility of using the most active compounds as fluorescent probes to determine tumours or their
[...] Read more.
The aims of this study were: (i) to explore the structure-activity relationship of some new anti-inflammatory benzothieno[3,2-d]pyrimidin-4-one sulphonamide thio-derivatives 111; and (ii) to evaluate the possibility of using the most active compounds as fluorescent probes to determine tumours or their progression. Therefore, to know the precise mechanism by which these compounds interact with cyclooxygenase (COX)-2 enzyme, a molecular docking study was carried out; to assess spectroscopic characteristics, their absorption and emission properties were determined. The results demonstrated that some derivatives of benzothieno[3,2-d] pyrimidine exhibit interesting anti-inflammatory properties related to interactions with active sites of COX-2 and are fluorescent. The antipyrine-bearing compound 4 displayed high COX-2 affinity (ΔG = −9.4) and good fluorescent properties (Φfl = 0.032). Thus, some members of this new class of anti-inflammatory may be promising for fluorescence imaging of cancer cells that express the COX-2 enzyme. Further in vitro and in vivo studies are needed to confirm this hypothesis. Full article
(This article belongs to the Special Issue Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry)
Open AccessArticle Cyclooxygenase-2 (COX-2) Inhibition Constrains Indoleamine 2,3-Dioxygenase 1 (IDO1) Activity in Acute Myeloid Leukaemia Cells
Molecules 2013, 18(9), 10132-10145; doi:10.3390/molecules180910132
Received: 4 July 2013 / Revised: 14 August 2013 / Accepted: 15 August 2013 / Published: 22 August 2013
Cited by 8 | PDF Full-text (897 KB) | HTML Full-text | XML Full-text
Abstract
Indoleamine 2,3-dioxygenase 1 (IDO1) metabolizes L-tryptophan to kynurenines (KYN), inducing T-cell suppression either directly or by altering antigen-presenting-cell function. Cyclooxygenase (COX)-2, the rate-limiting enzyme in the synthesis of prostaglandins, is over-expressed by several tumours. We aimed at determining whether COX-2 inhibitors down-regulate the
[...] Read more.
Indoleamine 2,3-dioxygenase 1 (IDO1) metabolizes L-tryptophan to kynurenines (KYN), inducing T-cell suppression either directly or by altering antigen-presenting-cell function. Cyclooxygenase (COX)-2, the rate-limiting enzyme in the synthesis of prostaglandins, is over-expressed by several tumours. We aimed at determining whether COX-2 inhibitors down-regulate the IFN-g-induced expression of IDO1 in acute myeloid leukaemia (AML) cells. IFN-γ at 100 ng/mL up-regulated COX-2 and IDO1 in HL-60 AML cells, both at mRNA and protein level. The increased COX-2 and IDO1 expression correlated with heightened production of prostaglandin (PG)E2 and kynurenines, respectively. Nimesulide, a preferential COX-2 inhibitor, down-regulated IDO1 mRNA/protein and attenuated kynurenine synthesis, suggesting that overall IDO inhibition resulted both from reduced IDO1 gene transcription and from inhibited IDO1 catalytic activity. From a functional standpoint, IFN-g-challenged HL-60 cells promoted the in vitro conversion of allogeneic CD4+CD25 T cells into bona fide CD4+CD25+FoxP3+ regulatory T cells, an effect that was significantly reduced by treatment of IFN-γ-activated HL-60 cells with nimesulide. Overall, these data point to COX-2 inhibition as a potential strategy to be pursued with the aim at circumventing leukaemia-induced, IDO-mediated immune dysfunction. Full article
(This article belongs to the Special Issue Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry)
Open AccessArticle Luteolin Inhibits Inflammatory Responses via p38/MK2/TTP-mediated mRNA Stability
Molecules 2013, 18(7), 8083-8094; doi:10.3390/molecules18078083
Received: 2 May 2013 / Revised: 3 July 2013 / Accepted: 4 July 2013 / Published: 9 July 2013
Cited by 10 | PDF Full-text (1372 KB) | HTML Full-text | XML Full-text
Abstract
Luteolin (Lut) is a common dietary flavonoid present in Chinese herbal medicines that has been reported to have important anti-inflammatory properties. The purposes of this study were to observe the inhibition of lipopolysaccharide (LPS)-induced inflammatory responses in bone marrow macrophages (BMM) by Lut,
[...] Read more.
Luteolin (Lut) is a common dietary flavonoid present in Chinese herbal medicines that has been reported to have important anti-inflammatory properties. The purposes of this study were to observe the inhibition of lipopolysaccharide (LPS)-induced inflammatory responses in bone marrow macrophages (BMM) by Lut, and to examine whether this inhibition involves p38/MK2/TTP-mediated mRNA stability. Lut suppressed the production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in a dose-dependent manner according to enzyme-linked immunosorbent assay (ELISA) analysis. Lut also shortened the half-lives of the TNF-α and IL-6 mRNAs according to real-time PCR analysis. Western blots were performed to assess the activation of p38 and MK2 as well as the expression of TTP. The results indicated that Lut inhibited p38 and MK2 phosphorylation while promoting TTP expression. These results suggest that the anti-inflammatory effects of Lut are partially mediated through p38/MK2/TTP-regulated mRNA stability. Full article
(This article belongs to the Special Issue Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry)
Open AccessArticle A Soft Coral Natural Product, 11-Episinulariolide Acetate, Inhibits Gene Expression of Cyclooxygenase-2 and Interleukin-8 through Attenuation of Calcium Signaling
Molecules 2013, 18(6), 7023-7034; doi:10.3390/molecules18067023
Received: 22 April 2013 / Revised: 30 May 2013 / Accepted: 13 June 2013 / Published: 17 June 2013
Cited by 4 | PDF Full-text (765 KB) | HTML Full-text | XML Full-text
Abstract
Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancer cells. EGFR-mediated signaling involves inflammatory gene expression including cyclooxygenase (COX)-2 and interleukin (IL)-8, and is associated with cancer pathogenesis. In a search of phytochemicals with anti-inflammatory activity, the COX-2 and IL-8
[...] Read more.
Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancer cells. EGFR-mediated signaling involves inflammatory gene expression including cyclooxygenase (COX)-2 and interleukin (IL)-8, and is associated with cancer pathogenesis. In a search of phytochemicals with anti-inflammatory activity, the COX-2 and IL-8 inhibitory activities of some marine compounds were examined. After screening these compounds 11-episinulariolide acetate (1) from soft coral exhibited the most potent activity. Reverse-transcription PCR; western blotting; ELISA and luciferase assays were used to test the effect of compound 1 on EGF-stimulated expressions of COX-2 and IL-8 in A431 human epidermoid carcinoma cells. After exposure to 10 μM of compound 1, expression levels of COX-2 and IL-8 were reduced. In addition; intracellular Ca2+ increase and Ca2+-dependent transcription factor activation were blocked by compound 1. Thus, compound 1 can potentially serve as a lead compound for targeting Ca2+ signaling-dependent inflammatory diseases. Full article
(This article belongs to the Special Issue Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry)
Open AccessArticle Indomethacin Inhibits Cancer Cell Migration via Attenuation of Cellular Calcium Mobilization
Molecules 2013, 18(6), 6584-6596; doi:10.3390/molecules18066584
Received: 18 March 2013 / Revised: 27 May 2013 / Accepted: 31 May 2013 / Published: 4 June 2013
Cited by 11 | PDF Full-text (2293 KB) | HTML Full-text | XML Full-text
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) were shown to reduce the risk of colorectal cancer recurrence and are widely used to modulate inflammatory responses. Indomethacin is an NSAID. Herein, we reported that indomethacin can suppress cancer cell migration through its influence on the focal complexes
[...] Read more.
Non-steroidal anti-inflammatory drugs (NSAIDs) were shown to reduce the risk of colorectal cancer recurrence and are widely used to modulate inflammatory responses. Indomethacin is an NSAID. Herein, we reported that indomethacin can suppress cancer cell migration through its influence on the focal complexes formation. Furthermore, endothelial growth factor (EGF)-mediated Ca2+ influx was attenuated by indomethacin in a dose dependent manner. Our results identified a new mechanism of action for indomethacin: inhibition of calcium influx that is a key determinant of cancer cell migration. Full article
(This article belongs to the Special Issue Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry)
Open AccessArticle The Ameliorative Effect of Sophoricoside on Mast Cell-Mediated Allergic Inflammation in Vivo and in Vitro
Molecules 2013, 18(5), 6113-6127; doi:10.3390/molecules18056113
Received: 11 March 2013 / Revised: 7 May 2013 / Accepted: 10 May 2013 / Published: 22 May 2013
Cited by 3 | PDF Full-text (1073 KB) | HTML Full-text | XML Full-text
Abstract
Sophoricoside exhibits numerous pharmacological effects, including anti- inflammatory and anti-cancer actions, yet the exact mechanism that accounts for the anti-allergic effects of sophoricoside is not completely understood. The aim of the present study was to elucidate whether and how sophoricoside modulates the mast
[...] Read more.
Sophoricoside exhibits numerous pharmacological effects, including anti- inflammatory and anti-cancer actions, yet the exact mechanism that accounts for the anti-allergic effects of sophoricoside is not completely understood. The aim of the present study was to elucidate whether and how sophoricoside modulates the mast cell-mediated allergic inflammation in vitro and in vivo. We investigated the pharmacological effects of sophoricoside on both compound 48/80 or histamine-induced scratching behaviors and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in mice. Additionally, to find a possible explanation for the anti-inflammatory effects of sophoricoside, we evaluated the effects of sophoricoside on the production of histamine and inflammatory cytokines and activation of nuclear factor-κB (NF-κB) and caspase-1 in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). The finding of this study demonstrated that sophoricoside reduced compound 48/80 or histamine-induced scratching behaviors and DNCB-induced atopic dermatitis in mice. Additionally, sophoricoside inhibited the production of inflammatory cytokines as well as the activation of NF-κB and caspase-1 in stimulated HMC-1. Collectively, the findings of this study provide us with novel insights into the pharmacological actions of sophoricoside as a potential molecule for use in the treatment of allergic inflammation diseases. Full article
(This article belongs to the Special Issue Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry)
Open AccessArticle Synthesis and Characterization of Celecoxib Derivatives as Possible Anti-Inflammatory, Analgesic, Antioxidant, Anticancer and Anti-HCV Agents
Molecules 2013, 18(3), 3595-3614; doi:10.3390/molecules18033595
Received: 31 January 2013 / Revised: 12 February 2013 / Accepted: 10 March 2013 / Published: 21 March 2013
Cited by 12 | PDF Full-text (336 KB) | HTML Full-text | XML Full-text
Abstract
A series of novel N-(3-substituted aryl/alkyl-4-oxo-1,3-thiazolidin-2-ylidene)-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamides 2ae were synthesized by the addition of ethyl a-bromoacetate and anhydrous sodium acetate in dry ethanol to N-(substituted aryl/alkylcarbamothioyl)-4-[5-(4-methylphenyl)-3-(trifluoro-methyl)-1H-pyrazol-1-yl]benzene sulfonamides 1ae, which were synthesized by the
[...] Read more.
A series of novel N-(3-substituted aryl/alkyl-4-oxo-1,3-thiazolidin-2-ylidene)-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamides 2ae were synthesized by the addition of ethyl a-bromoacetate and anhydrous sodium acetate in dry ethanol to N-(substituted aryl/alkylcarbamothioyl)-4-[5-(4-methylphenyl)-3-(trifluoro-methyl)-1H-pyrazol-1-yl]benzene sulfonamides 1ae, which were synthesized by the reaction of alkyl/aryl isothiocyanates with celecoxib. The structures of the isolated products were determined by spectral methods and their anti-inflammatory, analgesic, antioxidant, anticancer and anti-HCV NS5B RNA-dependent RNA polymerase (RdRp) activities evaluated. The compounds were also tested for gastric toxicity and selected compound 1a was screened for its anticancer activity against 60 human tumor cell lines. These investigations revealed that compound 1a exhibited anti-inflammatory and analgesic activities and further did not cause tissue damage in liver, kidney, colon and brain compared to untreated controls or celecoxib. Compounds 1c and 1d displayed modest inhibition of HCV NS5B RdRp activity. In conclusion, N-(ethylcarbamothioyl)-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (1a) may have the potential to be developed into a therapeutic agent. Full article
(This article belongs to the Special Issue Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry)
Open AccessArticle Anti-Inflammatory and Anti-Allergic Activities of Pentaherb Formula, Moutan Cortex (Danpi) and Gallic Acid
Molecules 2013, 18(3), 2483-2500; doi:10.3390/molecules18032483
Received: 10 January 2013 / Revised: 4 February 2013 / Accepted: 7 February 2013 / Published: 25 February 2013
Cited by 19 | PDF Full-text (500 KB) | HTML Full-text | XML Full-text
Abstract
Pentaherb formula (PHF) has been proven to improve the quality of life of children with atopic dermatitis without side effects. The aim of this study was to elucidate the potential anti-inflammatory and anti-allergic activities of PHF, Moutan Cortex (Danpi/DP) and gallic acid (GA)
[...] Read more.
Pentaherb formula (PHF) has been proven to improve the quality of life of children with atopic dermatitis without side effects. The aim of this study was to elucidate the potential anti-inflammatory and anti-allergic activities of PHF, Moutan Cortex (Danpi/DP) and gallic acid (GA) using human basophils (KU812 cells), which are crucial effector cells in allergic inflammation. PHF, DP and GA could significantly suppress the expression of allergic inflammatory cytokine IL-33-upregulated intercellular adhesion molecule (ICAM)-1, and the release of chemokines CCL2, CCL5, CXCL8 and inflammatory cytokine IL-6 from KU812 cells (all p < 0.05). With the combined use of dexamethasone (0.01 μg/mL) and GA (10 μg/mL), the suppression of ICAM-1 expression and CCL5 and IL-6 release of IL-33-activated KU812 cells were significantly greater than the use of GA alone (all p < 0.05). The suppression of the IL-33-induced activation of intracellular signalling molecules p38 mitogen activated protein kinase, nuclear factor-kB and c-Jun amino-terminal kinase in GA-treated KU812 cells could be the underlying mechanism for the suppression on ICAM-1, chemokines and cytokines. The combined use of dexamethasone with the natural products PHF or DP or GA might therefore enhance the development of a novel therapeutic modality for allergic inflammatory diseases with high potency and fewer side effects. Full article
(This article belongs to the Special Issue Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry)

Review

Jump to: Research

Open AccessReview Physiological Roles and Potential Therapeutic Applications of the P2X7 Receptor in Inflammation and Pain
Molecules 2013, 18(9), 10953-10972; doi:10.3390/molecules180910953
Received: 17 June 2013 / Revised: 26 August 2013 / Accepted: 27 August 2013 / Published: 5 September 2013
Cited by 35 | PDF Full-text (218 KB) | HTML Full-text | XML Full-text
Abstract
The P2X7 receptor (P2X7R) is a nonselective cation channel that is activated by extracellular ATP and triggers the secretion of several proinflammatory substances, such as IL-1β, IL-18, TNF-α, and nitric oxide. Recently, several preclinical studies have demonstrated that this receptor participates in inflammation
[...] Read more.
The P2X7 receptor (P2X7R) is a nonselective cation channel that is activated by extracellular ATP and triggers the secretion of several proinflammatory substances, such as IL-1β, IL-18, TNF-α, and nitric oxide. Recently, several preclinical studies have demonstrated that this receptor participates in inflammation and pain mechanisms. Taken together, these results indicate that P2X7R is a promising pharmacological target, and compounds that modulate the function of this receptor show potential as new anti-inflammatory medicines. In this review, we discuss aspects of P2X7R pharmacology and the participation of this protein in inflammation and pain and provide an overview of some promising compounds that have been tested as antagonists of P2X7R, with clinical applicability. Full article
(This article belongs to the Special Issue Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry)
Open AccessReview Natural Products as a Source of Anti-Inflammatory Agents Associated with Inflammatory Bowel Disease
Molecules 2013, 18(6), 7253-7270; doi:10.3390/molecules18067253
Received: 27 April 2013 / Revised: 5 June 2013 / Accepted: 14 June 2013 / Published: 19 June 2013
Cited by 26 | PDF Full-text (348 KB) | HTML Full-text | XML Full-text
Abstract
Accumulating epidemiological and clinical study indicates that inflammation is a significant risk factor to develop various human diseases such as inflammatory bowel disease (IBD), chronic asthma, rheumatoid arthritis, multiple sclerosis, and psoriasis. Suppressing inflammation is therefore important to control or prevent various diseases.
[...] Read more.
Accumulating epidemiological and clinical study indicates that inflammation is a significant risk factor to develop various human diseases such as inflammatory bowel disease (IBD), chronic asthma, rheumatoid arthritis, multiple sclerosis, and psoriasis. Suppressing inflammation is therefore important to control or prevent various diseases. Among them, IBD is one of the major problems affecting people worldwide. IBD affects at least one in a thousand persons in many Western countries. Various natural products have been shown to safely suppress pro-inflammatory pathway and control IBD. In vivo and/or in vitro studies indicate that anti-IBD effects of natural products occur by inhibition of the expression of pro-inflammatory cytokines (for example, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule expression and pro-inflammatory mediators (such as inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2), master transcription factors (such as nuclear factor-κB (NF-κB)), reactive oxygen species (ROS) and by improving the antioxidant activity. In this review, we summarize recent research focused on IBD and the effects that natural products have on IBD factors. Full article
(This article belongs to the Special Issue Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry)
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