Evolution of nonsteroidal anti-inflammatory drugs (NSAIDs): cyclooxygenase (COX) inhibition and beyond
P.N. Praveen Rao,Edward E. Knaus +1 more
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TLDR
This review traces the origins of NSAIDs, their mechanism of action at the molecular level such as cyclooxygenase (COX) inhibition, development of selective COX-2 inhibitors, their adverse cardiovascular effects, and some recent developments targeted to the design of effective anti-inflammatory agents with reduced side effects.Abstract:
Purpose. NSAIDs constitute an important class of drugs with therapeutic applications that have spanned several centuries. Treatment of inflammatory conditions such as rheumatoid arthritis (RA) and osteoarthritis (OA) starting from the classic drug aspirin to the recent rise and fall of selective COX-2 inhibitors has provided an enthralling evolution. Efforts to discover an ultimate magic bullet to treat inflammation continues to be an important drug design challenge. This review traces the origins of NSAIDs, their mechanism of action at the molecular level such as cyclooxygenase (COX) inhibition, development of selective COX-2 inhibitors, their adverse cardiovascular effects, and some recent developments targeted to the design of effective anti-inflammatory agents with reduced side effects. Methods. Literature data is presented describing important discoveries pertaining to the sequential development of classical NSAIDs and then selective COX-2 inhibitors, their mechanism of action, the structural basis for COX inhibition, and recent discoveries. Results. A brief history of the development of NSAIDs and the market withdrawal of selective COX-2 inhibitors is explained, followed by the description of prostaglandin biosynthesis, COX isoforms, structure and function. The structural basis for COX-1 and COX-2 inhibition is described along with methods used to evaluate COX-1/COX-2 inhibition. This is followed by a section that encompasses the major chemical classes of selective COX-2 inhibitors. The final section describes briefly some of the recent advances toward developing effective anti-inflammatory agents such as nitric oxide donor NO-NSAIDs, dual COX/LOX inhibitors and anti-TNF therapy. Conclusions. A great deal of progress has been made toward developing novel anti-inflammatory agents. In spite of the tremendous advances in the last decade, the design and development of a safe, effective and economical therapy for treating inflammatory conditions still presents a major challenge.read more
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Nonsteroidal anti-inflammatory drugs and pain in cancer patients: a systematic review and reappraisal of the evidence
David J. Magee,David J. Magee,Shaman Jhanji,Shaman Jhanji,George Poulogiannis,Paul Farquhar-Smith,Matthew R.D. Brown,Matthew R.D. Brown +7 more
TL;DR: There is a lack of high-quality evidence regarding the analgesic efficacy of NSAIDs in cancer pain, with short study durations and heterogeneity in outcome measures limiting the ability to draw meaningful conclusions.
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Identification of New Rofecoxib-Based Cyclooxygenase-2 Inhibitors: A Bioinformatics Approach
Rozires P Leão,Josiane V Cruz,Glauber V da Costa,Jorddy Neves Cruz,Elenilze F B Ferreira,Rai C. Silva,Rai C. Silva,Lúcio R de Lima,Rosivaldo S. Borges,Gabriela Bianchi dos Santos,Cleydson B. R. Santos +10 more
TL;DR: Future in vitro and in vivo studies are needed to confirm the anti-inflammatory potential of the compounds selected here with bioinformatics approaches based on rofecoxib ligand, which showed satisfactory pharmacokinetic results related to absorption and distribution.
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Symposium review: Oxylipids and the regulation of bovine mammary inflammatory responses
TL;DR: The bovine inflammatory response and the role that oxylipids play in contributing to the onset and resolution of inflammation especially as it pertains to mastitis are described.
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Anti-inflammatory effects of apo-9'-fucoxanthinone from the brown alga, Sargassum muticum.
TL;DR: This is the first report describing effective anti-inflammatory activity for apo-9’-fucoxanthinone′-fu Coxanthnone isolated from S. muticum, and may be a good candidate for delaying the progression of human inflammatory diseases and warrants further studies.
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Pharmacological profile and efficiency in vivo of diflapolin, the first dual inhibitor of 5-lipoxygenase-activating protein and soluble epoxide hydrolase.
Ulrike Garscha,Erik Romp,Simona Pace,Antonietta Rossi,Veronika Temml,Daniela Schuster,Stefanie König,Jana Gerstmeier,Stefanie Liening,Markus Werner,Heiner Atze,Sandra K. Wittmann,Christina Weinigel,Silke Rummler,Gerhard K. E. Scriba,Lidia Sautebin,Oliver Werz +16 more
TL;DR: Diflapolin is a highly active dual FLAP/sEH inhibitor in vitro and in vivo with target specificity to treat inflammation-related diseases.
References
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Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs
TL;DR: Experiments with guinea-pig lung suggest that some of the therapeutic effects of sodium salicylate and aspirin-like drugs are due to inhibition of the synthesis of prostaglandins.
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Comparison of Upper Gastrointestinal Toxicity of Rofecoxib and Naproxen in Patients with Rheumatoid Arthritis
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TL;DR: In patients with rheumatoid arthritis, treatment with rofecoxib, a selective inhibitor of cyclooxygenase-2, is associated with significantly fewer clinically important upper gastrointestinal events than treatment with naproxen, a nonselective inhibitor.
Journal ArticleDOI
Gastrointestinal Toxicity With Celecoxib vs Nonsteroidal Anti-inflammatory Drugs for Osteoarthritis and Rheumatoid Arthritis: The CLASS Study: A Randomized Controlled Trial
Fred E. Silverstein,Gerald A. Faich,Jay L. Goldstein,Lee S. Simon,Theodore Pincus,Andrew Whelton,Robert W. Makuch,Glenn M. Eisen,Naurang M. Agrawal,William F. Stenson,Aimee M. Burr,William W. Zhao,Jeffrey D. Kent,James B. Lefkowith,Kenneth M. Verburg,G. Steven Geis +15 more
TL;DR: In this study, celecoxib, at dosages greater than those indicated clinically, was associated with a lower incidence of symptomatic ulcers and ulcer complications combined, as well as other clinically important toxic effects, compared with NSAIDs at standard dosages.
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Cyclooxygenases: Structural, cellular, and molecular biology
TL;DR: This review examines how the structures of these enzymes relate mechanistically to cyclooxygenase and peroxidase catalysis, and how differences in the structure of PGHS-2 confer on this isozyme differential sensitivity to COX-2 inhibitors.
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Cyclooxygenases 1 and 2
TL;DR: The discovery ofCOX-2 has made possible the design of drugs that reduce inflammation without removing the protective PGs in the stomach and kidney made by COX-1, which may not only be anti-inflammatory but may also be active in colon cancer and Alzheimer's disease.