Abstract:
:Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs worldwide. Nevertheless, their intake is frequently associated with gastrointestinal side effects, representing still an important medical and socio-economic problem. In recent years efforts focused on the development of highly selective COX-2 inhibitors with an improved gastric tolerability profile. However, severe cardiovascular adverse reactions challenged the initial enthusiasm in this new class of anti-inflammatory drugs. In addition, the market withdrawals of some coxibs led to a relative reluctance in prescribing COX-2 inhibitors in clinical practice. As a consequence, the interest for alternative approaches to reduce gastrointestinal side effects associated with NSAIDs has re-emerged. There are two main components of gastric damaging properties of NSAIDs: (1) the acute toxicity associated with the short-term intake of NSAIDs, which is principally caused by local irritation of the gastric mucosa (2) the chronic toxicity resulting mainly from systemic effects associated with prolonged administration of NSAIDs. Based on that background two different approaches were pursued in the search for GI sparing NSAIDs: a) modification of classical NSAIDs by associating them with phospholipids, cyclodextrins, or chemical moieties that release gastroprotective mediators and b) defining novel targets as well as developing new compounds like dual COX/5-LO or mPGES-1 inhibitors. This review provides the first comprehensive overview of all currently applied approaches taken to improve the risk-benefit ratio of NSAIDs focusing on the structure activity relationships and the respective mechanism of action underlying the individual approaches. The insight gained in this review is useful for further research activity in this field.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Abdel-Tawab M,Zettl H,Schubert-Zsilavecz Mdoi
10.2174/092986709788682209subject
Has Abstractpub_date
2009-01-01 00:00:00pages
2042-63issue
16eissn
0929-8673issn
1875-533Xjournal_volume
16pub_type
杂志文章,评审abstract::The utilization of graphene-based nanomaterials combined with magnetic nanoparticles offers key benefits in the modern biomedicine. In this minireview, we focus on the most recent advances in hybrids of magnetic graphene derivatives for biomedical applications. We initially analyze the several methodologies employed f...
journal_title:Current medicinal chemistry
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doi:10.2174/0929867323666161216144218
更新日期:2017-01-01 00:00:00
abstract::Combination therapy in the treatment of viral infections in which, for example, three different drugs against three different targets on three independent proteins are administered, has been highly successful clinically. However, it is only a matter of time before a virus will arise resistant to all three drugs, becau...
journal_title:Current medicinal chemistry
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abstract::The COVID-19 pandemic has had catastrophic Global effects on financial markets, jobs and peoples' lives. Future prevention/therapy of COVID-19 will rely heavily on vaccine development and attempts to repurpose drugs previously used for other microbial diseases. Little attention, however, has been paid to possible diff...
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doi:10.2174/0929867327666201027152400
更新日期:2020-10-27 00:00:00
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journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712801215883
更新日期:2012-01-01 00:00:00
abstract::The alphavbeta3 receptor, which are members of the group of the cellular adhesion molecules (CAM), are heterodimeric transmembrane glycoprotein receptors involved in processes such as cell-cell and cell-matrix adhesion, cell migration and signaling. Integrin alphavbeta3 receptor is expressed on almost all cells origin...
journal_title:Current medicinal chemistry
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doi:10.2174/0929867053363522
更新日期:2005-01-01 00:00:00
abstract::Recent results using animal models of inflammatory skin conditions have shown that blockers of the voltage-gated potassium channel, Kv1.3 hold great promise for clinical utility. Kv1.3 blockers act as immunosuppressants by modulating the various subsets of inflammatory T and B cells involved in autoimmune disorders. W...
journal_title:Current medicinal chemistry
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doi:10.2174/092986710792065072
更新日期:2010-01-01 00:00:00
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journal_title:Current medicinal chemistry
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更新日期:2007-01-01 00:00:00
abstract:OBJECTIVES:Post-exercise cardiac troponin T (cTnT) release has been widely reported in adult athletes but limited data is available for adolescents. The aim of this study was to determine the incidence and magnitude of cTnT appearance in a large group of adolescent runners, and to determine any association between cTnT...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/092986711796642625
更新日期:2011-01-01 00:00:00
abstract::Many non-cardiovascular drugs of common clinical use cause, as an unwanted accessory property, the prolongation of the cardiac repolarisation process, due to the block of the HERG (Human Ether-a-go-go Related Gene) potassium channel, responsible for the repolarising I(Kr) current. This delayed cardiac repolarisation p...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2004-10-01 00:00:00
abstract::Inflammation plays a critical role in the atherosclerotic process in various vascular beds, starting from endothelial dysfunction and counting all stages of plaque development. The significant contribution of inflammation in the initiation and progression of atherosclerosis has been documented over many years but its ...
journal_title:Current medicinal chemistry
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更新日期:2015-01-01 00:00:00
abstract::In their structural multiplicity and in the extent to which they occur in nature the derivatives of benzofuran are significantly lesser than the isoelectronic analogue indoles. However, these heterocyclic compounds show a variety of pharmacological properties, and change of their structure offers a high degree of dive...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709787002826
更新日期:2009-01-01 00:00:00
abstract::The oxime formation reaction of therapeutical progestogen (levonorgestrel, levonorgestrel acetate, norethisterone), androgen (methyltestosterone, testosterone phenylpropionate) and anabolic (nortestosterone phenylpropionate) Delta(4)-3-ketosteroids has been investigated. The ketosteroid-hydroxylamine reaction was moni...
journal_title:Current medicinal chemistry
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doi:10.2174/0929867013372238
更新日期:2001-09-01 00:00:00
abstract::The evidence seems to be growing in favor of the stem cell theory of cancer with the emergence of studies demonstrating the parallel mechanisms of self renewing pathways in stem cells and particular subsets of cancer cells. The finding of leukemia stem cells and subsequently breast cancer stem cells (BCSC) further sup...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712804485863
更新日期:2012-01-01 00:00:00
abstract::Obesity and metabolic syndrome represent major public health problems, and are the biggest preventable causes of death worldwide. Obesity is the leading risk factor for type 2 diabetes mellitus (T2DM), cardiovascular diseases and non-alcoholic fatty liver disease. Obesity-associated insulin resistance, which is charac...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867311320210001
更新日期:2013-01-01 00:00:00
abstract::Lipopolysaccharide (LPS), which constitutes the lipid portion of the outer leaflet of Gram-negative bacteria, is essential for growth. It is also responsible for the variety of biological effects associated with Gram-negative sepsis. Recent advances have elucidated the exact chemical structure of this highly complex m...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986711794927676
更新日期:2011-01-01 00:00:00
abstract::ATP-sensitive K(+) channels (K(ATP)channels) regulate insulin secretion by coupling intracellular metabolic changes to excitability of the plasma membrane in pancreatic beta-cells. The channels are closed when extracellular glucose levels are elevated due to enhanced feature. By contrast, cardiac-type K(ATP) channels,...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867033368475
更新日期:2003-02-01 00:00:00
abstract:BACKGROUND:With global increase in elderly population, modern societies must find strategies to reduce the consequences of aging process; thereby decreasing the incidence of age-related neurodegenerative diseases. Oxidative stress and recently inflammation, have been pointed out as the leading causes of brain aging. Th...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170724102743
更新日期:2017-01-01 00:00:00
abstract::Obesity, associated with a series of complications such as diabetes, hypertension, and heart disease, is a great threat to human health and leads to increased morbidity and mortality. Despite the presence of anti-obesity agents on the market, the application of these drugs is limited because of their typical side effe...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867326666190215114359
更新日期:2020-01-01 00:00:00
abstract::Ion channel dysfunction has been identified as a contributor to symptom development and neurodegeneration in multiple sclerosis (MS). The molecular insights have been translated into new lines of research, with ion channel modulation now representing a therapeutic approach in MS. Studies of Na+ channel function have d...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867322666151029104452
更新日期:2015-01-01 00:00:00
abstract::Chemoprevention is based on the use of non-toxic, pharmacologically active agents to prevent tumor progression. In this regard, natural dietary agents have been described by the most recent literature as promising tools for controlling onset and progression of malignancies. Extensive research has been so far performed...
journal_title:Current medicinal chemistry
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doi:10.2174/0929867325666180629153141
更新日期:2020-01-01 00:00:00
abstract::Nature as a source of inspiration has been shown to have a great beneficial impact on the development of new computational methodologies. In this scenario, analyses of the interactions between a protein target and a ligand can be simulated by biologically inspired algorithms (BIAs). These algorithms mimic biological s...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986711795029573
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:The incidence of pancreatic cancer (PC) is rising in parallel with the deaths caused by this malignant disease largely due to limited improvement in current treatment strategies. In spite of aggressive PC research, for the past three decades, there has been no significant improvement in the five-year surviva...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170209104453
更新日期:2018-01-01 00:00:00
abstract::The hemostatic system comprises platelet aggregation, coagulation and fibrinolysis also termed primary, secondary and tertiary hemostasis. From the platelet transcriptome 6000 mRNA species and represent receptors, ion channels, signalling molecules, kinases, phosphatases, and structural, metabolic and regulatory prote...
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pub_type: 杂志文章,评审
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更新日期:2004-09-01 00:00:00
abstract:BACKGROUND:Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is the leading cause of cryptogenic cirrhosis and has consistently been implicated in related metabolic disorders, such as dyslipidemia and type 2 diabetes (T2D). However, the pathogenesis of NAFLD remains to be elucidated, and ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2018-01-01 00:00:00
abstract::Nature continues to be the main source of inspiration for synthetic chemists in their quest to make novel conjugates, which can have different physical, biological and medicinal properties. Nature makes these conjugates from mixed biosynthesis and some of these chimeras are found to exhibit unusual biological properti...
journal_title:Current medicinal chemistry
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更新日期:2006-01-01 00:00:00
abstract::Ten years elapsed since the discovery by Sanofi of SR141716A the first selective CB(1) cannabinoid receptor antagonist. Shortly after, Sanofi also reported the synthesis of the first selective CB(2) cannabinoid receptor antagonist, SR144528. Since these two milestones in the cannabinoid field, many other compounds, mo...
journal_title:Current medicinal chemistry
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更新日期:2005-01-01 00:00:00
abstract::Vitamins are dietary components which are necessary for life. They play a major role in health and their deficiency may be linked to symptoms of psychiatric disorders. B vitamins are required for proper functioning of the methylation cycle, monoamine oxidase production, DNA synthesis and the repair and maintenance of ...
journal_title:Current medicinal chemistry
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更新日期:2016-01-01 00:00:00
abstract::Drug resistance is one of the major obstacles limiting the success of cancer chemotherapy. Biological mechanisms contributing to drug resistance may be present de novo and related to inherent features or may be raised after exposure to anticancer drugs. In recent years, both clinical observations and experimental stud...
journal_title:Current medicinal chemistry
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更新日期:2011-01-01 00:00:00
abstract::Although the renin-angiotensin system (RAS) is already an old acquaintance, there are often exciting discoveries that improve our knowledge of it and open new therapeutic possibilities. Moreover, well-established drugs, such as angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), or be...
journal_title:Current medicinal chemistry
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更新日期:2013-01-01 00:00:00
abstract::Selenium is an essential trace element. It is, however toxic at concentration little above which is required for health. Selenium is incorporated into proteins as selenocysteine, the 21(st) amino acid. Selenoproteins are found in bacteria, archaea and eukaryotes. Biochemical and physicochemical properties of selenium ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867043365053
更新日期:2004-06-01 00:00:00