Synthesis and Docking study of some bioactive N-(benzo[d]thiazol-2-yl)-2- (4-((substituted)phenoxy)acetamide on Cyclo-oxygenase-2 enzyme and invivo analgesic activity evaluation

2020 ◽  
Vol 17 ◽  
Author(s):  
Sumit Kumar ◽  
Arvind Kumar ◽  
Amit Verma ◽  
Arun Kumar Mishra
Keyword(s):  
Biological Activity ◽  
Catalytic Amount ◽  
Docking Study ◽  
Analgesic Effects ◽  
Benzothiazole Derivatives ◽  
Commercially Important ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Pharmacologically Active ◽  
Cox 2 Inhibitors

Background:: The benzothiazole and its derivatives reported an extremely key duty in the progress of commercially important intermediary molecules, which are wanted for the manufacture of various pharmacologically active agents. Introduction:: As a necessary element of ongoing examination for the synthesis of new Nonsteroidal anti-inflammatory agents (NSAIDs), a number of new benzothiazole derivatives were taken under thought for synthesis and were computationally studied along with biological activity. Methods:: Obtainable benzothiazole derivatives were synthesized by the condensing of 2-(4-aminophenoxy)-N- (benzo[d]thiazol-2-yl)acetamide with substituted acetophenones in ethanol in the presence of catalytic amount of glacial acetic acid. The structures of newly synthesized compounds were characterized by IR, NMR spectroscopy and elemental analysis techniques. Several molecular properties of these derivatives were computed in order to estimate their drug like candidates. Molecular docking was performed to these synthesized derivatives with particular reference to cyclooxygenase- 2 (COX-2) enzyme. The synthesized derivatives were screened for their biological activity, including analgesic and antiinflammatory activity as COX-2 inhibitors. Results and Discussion:: From all data, it established that among all target compounds, S-4 (N-(benzo[d]thiazol-2-yl)-2-(4- ((1-(3-nitrophenyl)ethylidene)amino) phenoxy)acetamide) displayed the highest anti-inflammatory and analgesic effects. Conclusion:: All these findings recommended that S-4 might be utilized as a promising new lead compound for Nonsteroidal anti-inflammatory drug (NSAIDs) development.

scholarly journals Mechanisms of Nonsteroidal Anti-Inflammatory Drug-Induced Gastrointestinal Injury and Repair: A Window of Opportunity for Cyclooxygenase-Inhibiting Nitric Oxide Donors

2004 ◽  
Vol 18 (4) ◽  
pp. 229-236 ◽  
Author(s):  
Rafael Perini ◽  
Stefano Fiorucci ◽  
John L Wallace
Keyword(s):  
Nitric Oxide ◽  
Platelet Aggregation ◽  
Ulcer Healing ◽  
Significant Risk ◽  
Nitric Oxide Donors ◽  
Drug Induced ◽  
Analgesic Effects ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause damage in the upper gastrointestinal (GI) tract by impairing the ability of the mucosa to resist and respond to injury. Many of these effects of NSAIDs can be attributed to their ability to suppress mucosal prostaglandin synthesis. Selective inhibitors of cyclooxygenase (COX)-2 are less likely to disrupt mucosal defence and do not interfere with platelet aggregation. Thus, their use is associated with a reduced incidence of serious GI adverse events; however, a significant risk of such events still persists. At least in animal models, selective COX-2 inhibitors interfere with ulcer healing to the same extent as conventional NSAIDs. In contrast, COX-inhibiting nitric oxide donors (CINODs) produce anti-inflammatory and analgesic effects comparable or superior to those of NSAIDs, but with greatly reduced GI toxicity. Unlike NSAIDs and selective COX-2 inhibitors, CINODs do not interfere with ulcer healing. Moreover, because CINODs suppress the activity of both COX-1 and COX-2, they do not share with selective COX-2 inhibitors the lack of cardioprotection afforded by significant suppression of platelet aggregation. Because of their safety profile, CINODs may be particularly useful for long term prevention applications, such as for colon cancer, cardiovascular disease and Alzheimer's disease.

scholarly journals Non-steroidal anti-inflammatory drugs: an overview

2019 ◽  
Vol 9 (1-s) ◽  
pp. 442-448 ◽  
Author(s):  
Kasturi Jahnavi ◽  
Palla Pavani Reddy ◽  
Bakshi Vasudha ◽  
Boggula Narender
Keyword(s):  
Side Effects ◽  
Gastrointestinal Haemorrhage ◽  
Cyclooxygenase Inhibitors ◽  
Full Spectrum ◽  
Analgesic Effects ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Musculoskeletal Trauma ◽  
Cox 2 Inhibitors

Non-steroidal anti-inflammatory drugs (NSAIDs) including both traditional non-selective NSAIDs and the selective cyclooxygenase (COX)-2 inhibitors, are widely used for their anti-inflammatory and analgesic effects. NSAIDs are a necessary choice in pain management because of the integrated role of the COX path way in the generation of inflammation and in the biochemical recognition of pain. NSAIDs are the competitive inhibitors of cyclooxygenase (COX), the enzyme which mediates the bioconversion of arachidonic acid to inflammatory prostaglandins (PGs). Their use is associated with the side effects such as gastrointestinal and renal toxicity. They are the most commonly employed first line drugs for all these conditions and many others-like musculoskeletal trauma, minor aches and pains, and dysmenorrhoea. The therapeutic anti-inflammatory action of NSAIDs is produced by the inhibition of COX-2, while the undesired side effects arise from inhibition of COX-1 activity. Thus, it was though those more selective COX-2 inhibitors would have reduced side effects. Based upon a number of selective COX-2 inhibitors (Rofecoxib, Celecoxib etc.) were developed as safer NSAIDs with improved gastric safety profile. Several newer applications like prophylaxis of stroke with aspirin are now common place. Use of these drugs for the prophylaxis of conditions like Alzheimer’s disease and colorectal cancer is being evaluated. Unfortunately, they have several toxicities ranging from minor heartburn to severe gastrointestinal haemorrhage and perforation. Therefore, newer NSAIDs have been introduced in recent years to circumvent this problem. In preliminary studies, these have shown better safety, efficacy, and tolerability but the full spectrum of adverse reactions of these drugs is yet to be fully known. This review can be used for further research as well as clinical purpose. Keywords: Non-steroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase inhibitors, prostaglandins, aspirin.

scholarly journals Flunixin Meglumine Reduces Milk Isoprostane Concentrations in Holstein Dairy Cattle Suffering from Acute Coliform Mastitis

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 834
Author(s):  
Carsten C. F. Walker ◽  
Jill L. Brester ◽  
Lorraine M. Sordillo
Keyword(s):  
Medical Intervention ◽  
Systemic Involvement ◽  
Analgesic Effects ◽  
Markers Of Inflammation ◽  
Inflammatory Mediator Production ◽  
Flunixin Meglumine ◽  
Coliform Mastitis ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Oxidant Status

Dysfunctional inflammation contributes significantly to the pathogenesis of coliform mastitis and the classical pro-inflammatory enzyme cyclooxygenase-2 (COX-2) is the target of medical intervention using the non-steroidal anti-inflammatory drug (NSAID) flunixin meglumine (FM). Inhibition of COX-2 by FM can decrease concentrations of pro-inflammatory fatty acid-based mediators called eicosanoids, providing antipyretic and analgesic effects in dairy cows suffering from coliform mastitis. However, approximately 50% of naturally occurring coliform mastitis with systemic involvement results in death of the animal, even with NSAID treatment. Inadequate antioxidant potential (AOP) to neutralize reactive oxygen species (ROS) produced during excessive inflammation allows for oxidative stress (OS), contributing to tissue damage during coliform mastitis. Biomarkers of lipid peroxidation by ROS, called isoprostanes (IsoP), were used in humans and cattle to quantify the extent of OS. Blood IsoP were shown to be elevated and correlate with oxidant status during acute coliform mastitis. However, the effect of FM treatment on oxidant status and markers of OS has not been established. Blood IsoP concentrations were used to quantify systemic OS, whereas milk was used to assess local OS in the mammary gland. Results indicate that FM treatment had no effect on blood markers of inflammation but reduced the oxidant status index (OSi) by increasing blood AOP from pre- to post-FM treatment. Milk AOP significantly increased from pre- to post-FM treatment, whereas ROS decreased, resulting in a decreased OSi from pre- to post-FM treatment. The only blood IsoP concentration that was significantly different was 5-iso-iPF2α-VI, with a decreased concentration from pre- to post-FM treatment. Conversely, milk 5-iso-iPF2α-VI, 8,12-iso-iPF2α-VI, and total IsoP concentrations were decreased following FM treatment. These results indicated that administration of FM did improve systemic and local oxidant status and reduced local markers of OS. However, differential effects were observed between those animals that survived the infection and those that died, indicating that pre-existing inflammation and oxidant status greatly affect efficacy of FM and may be the key to reducing severity and mortality associated with acute coliform infections. Supplementation to improve AOP and anti-inflammatory mediator production may significantly improve efficacy of FM treatment.

The role of celecoxib as a potential inhibitor in the treatment of inflammatory diseases - a review

2021 ◽  
Vol 28 ◽  
Author(s):  
Josiane Viana Cruz ◽  
Joaquín María Campos Rosa ◽  
Njogu Mark Kimani ◽  
Silvana Giuliatti ◽  
Cleydson Breno Rodrigues dos Santos
Keyword(s):  
Side Effects ◽  
Inflammatory Diseases ◽  
Structural Basis ◽  
Potential Inhibitor ◽  
Cyclooxygenase 1 ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors

: This article presents a simplified view of celecoxib as a potential inhibitor in the treatment of inflammatory diseases. The enzyme cyclooxygenase (COX) has, predominantly, two isoforms called cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). The former plays a constitutive role that is related to homeostatic effects in renal and platelets, while the latter is mainly responsible for induction of inflammatory effects. Since COX-2 plays an important role in the pathogenesis of inflammatory diseases, it has been signaled as a target for the planning of anti-inflammatory intermediates. Many inhibitors developed and planned for COX-2 inhibition have presented side effects to humans, mainly in the gastrointestinal and/or cardiovascular tract. Therefore, it is necessary to design new potential COX-2 inhibitors, which are relatively safe and without side effects. To this end, of the generation of non-steroidal anti-inflammatory drugs from “coxibs”, celecoxib is the only potent selective COX-2 inhibitor that is still commercially available. Thus, the compound celecoxib became a commercial prototype inhibitor for the development of anti-inflammatory agents for COX-2 enzyme. In this review, we provide highlights where such inhibition should provide a structural basis for the design of promising new non-steroidal anti-inflammatory drugs (NSAIDs) which act as COX-2 inhibitors with lesser side effects on the human body.

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