Faculty Opinions recommendation of Anti-inflammatory activity of monogalactosyldiacylglycerol in human articular cartilage in vitro: activation of an anti-inflammatory cyclooxygenase-2 (COX-2) pathway.

Objective: The inflammation and oxidative stress were related together in the generation of reactive oxygen species, which is responsible for the enhancement of inflammation associated with various chronic diseases. Methods: The aim of this study is to synthezise and characterizes the flavones (2-phenyl-1-benzopyran-4-one) derivatives and analyzed by their docking hypothetical data as an effective anti-inflammatory mediator against cyclooxygenase-2 (COX-2) enzyme. Further, the evaluation of various in vitro antioxidant and anti-inflammatory studies was carried out. Results: The 10 compounds were synthesized and characterized by ultraviolet, infrared, nuclear magnetic resonance, and mass spectroscopic techniques. The docking data results of these 10 flavones derivatives against COX-2 enzymes (Protein Data Bank ID: 3LN1) showed the binding energy ranging between −5.53 kcal/mol and −7.02 kcal/mol when compared with that of the standard diclofenac (−6.34 kcal/mol). The in vitro studies suggest that the lipophilic character of the side chain donor, along with the hydroxyl substituted flavones found to have significant half maximal inhibitory concentration values. Conclusion: Based on these in silico and in vitro evaluation results, these synthesized compounds could act as a promising inhibitor to target the COX- 2 enzyme. Hence, those compounds were effective in the management of chronic diseases by exhibits free radical scavenging and anti-inflammatory property.

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In-vitro anti-inflammatory activity ofPinus sylvestrisandPlantago lanceolataextracts: effect on inducible NOS, COX-1, COX-2 and their products in J774A.1 murine macrophages

Journal of Pharmacy and Pharmacology ◽

10.1211/0022357055605 ◽

2005 ◽

Vol 57 (3) ◽

pp. 383-391 ◽

Cited By ~ 20

Author(s):

E. Vigo ◽

A. Cepeda ◽

O. Gualillo ◽

R. Perez-Fernandez

Keyword(s):

Inflammatory Activity ◽

Murine Macrophages ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 1 ◽

Inducible Nos

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In vitro anti-inflammatory activity of carvacrol: Inhibitory effect on COX-2 catalyzed prostaglandin E2 biosynthesisb

Archives of Pharmacal Research ◽

10.1007/s12272-009-1120-6 ◽

2009 ◽

Vol 32 (1) ◽

pp. 75-78 ◽

Cited By ~ 74

Author(s):

Premysl Landa ◽

Ladislav Kokoska ◽

Marie Pribylova ◽

Tomas Vanek ◽

Petr Marsik

Keyword(s):

Prostaglandin E2 ◽

Inhibitory Effect ◽

Inflammatory Activity ◽

Cox 2 ◽

Anti Inflammatory

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Study of Osteoarthritis Treatment with Anti-Inflammatory Drugs: Cyclooxygenase-2 Inhibitor and Steroids

BioMed Research International ◽

10.1155/2015/595273 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 25

Author(s):

Hongsik Cho ◽

Andrew Walker ◽

Jeb Williams ◽

Karen A. Hasty

Keyword(s):

Gene Expression ◽

Type Ii Collagen ◽

Cartilage Degradation ◽

Cyclooxygenase 2 ◽

Cox Inhibitor ◽

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory

Patients with osteoarthritis (OA), a condition characterized by cartilage degradation, are often treated with steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) selective NSAIDs. Due to their inhibition of the inflammatory cascade, the drugs affect the balance of matrix metalloproteinases (MMPs) and inflammatory cytokines, resulting in preservation of extracellular matrix (ECM). To compare the effects of these treatments on chondrocyte metabolism, TNF-αwas incubated with cultured chondrocytes to mimic a proinflammatory environment with increasing production of MMP-1 and prostaglandin E2 (PGE2). The chondrocytes were then treated with either a steroid (prednisone), a nonspecific COX inhibitor NSAID (piroxicam), or a COX-2 selective NSAID (celecoxib). Both prednisone and celecoxib decreased MMP-1 and PGE-2 production while the nonspecific piroxicam decreased only the latter. Both prednisone and celecoxib decreased gene expression of MMP-1 and increased expression of aggrecan. Increased gene expression of type II collagen was also noted with celecoxib. The nonspecific piroxicam did not show these effects. The efficacy of celecoxibin vivowas investigated using a posttraumatic OA (PTOA) mouse model.In vivo, celecoxib increases aggrecan synthesis and suppresses MMP-1. In conclusion, this study demonstrates that celecoxib and steroids exert similar effects on MMP-1 and PGE2 productionin vitroand that celecoxib may demonstrate beneficial effects on anabolic metabolismin vivo.

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Studies in 3,4-diaryl-1,2,5-oxadiazoles and their N-oxides: Search for better COX-2 inhibitors

Acta Pharmaceutica ◽

10.2478/v10007-007-0002-z ◽

2007 ◽

Vol 57 (1) ◽

pp. 13-30 ◽

Cited By ~ 20

Author(s):

Mange Yadav ◽

Shrikant Shirude ◽

Devendra Puntambekar ◽

Pinkal Patel ◽

Hetal Prajapati ◽

...

Keyword(s):

Enzyme Inhibition ◽

Docking Studies ◽

Inflammatory Activity ◽

Rat Paw Edema ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 2 Inhibitors ◽

Cox 1

Studies in 3,4-diaryl-1,2,5-oxadiazoles and theirN-oxides: Search for better COX-2 inhibitorsA series of 3,4-diaryl-1,2,5-oxadiazoles and 3,4-diaryl-1,2,5-oxadiazoleN-oxides were prepared and evaluated for COX-2 and COX-1 binding affinityin vitroand for anti-inflammatory activity by the rat paw edema method.p-Methoxy (p-OMe) substituted compounds 9, 21, 34, 41, 42 showed COX-2 enzyme inhibition higher than that showed by compounds with other substituents. 3,4-Di(4-methoxyphenyl)-1,2,5-oxadiazoleN-oxide (42) showed COX-2 enzyme inhibition of 54% at 22 μmol L-1and COX-1 enzyme inhibition of 44% at 88 μmol L-1concentrations, but showed very lowin vivoanti-inflammatory activity. Its deoxygenated derivative (21) showed lower COX-2 enzyme inhibition (26% at 22 μmol L-1) and higher COX-1 enzyme inhibition (53% at 88 μmol L-1) but, markedin vivoanti-inflammatory activity (71% at 25 mg kg-1)vs.celecoxib (48% at 12.5 mg kg-1). Molecular modeling (docking) studies showed that the methoxy group is positioned in the vicinity of COX-2 secondary pocket and it also participates in hydrogen bonding interactions in the COX-2 active site. These preliminary studies suggest thatp-methoxy (p-OMe) group in one of benzene rings may give potentially active leads in this series of oxadiazole/N-oxides.

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Bacopamonnieri (L.) exerts anti-inflammatory effects on cells of the innate immune system in vitro

Food & Function ◽

10.1039/c3fo60467e ◽

2014 ◽

Vol 5 (3) ◽

pp. 517-520 ◽

Cited By ~ 10

Author(s):

Roderick Williams ◽

Gerald Münch ◽

Erika Gyengesi ◽

Louise Bennett

Keyword(s):

Immune System ◽

Acute Pain ◽

Innate Immune System ◽

Selective Inhibition ◽

Innate Immune ◽

Inflammatory Activity ◽

Consequent Reduction ◽

Cox 2 ◽

Anti Inflammatory

Bacopa monnieri(L., BM) is a traditional Ayurvedic medicinal herb recognised for its efficacy in relieving acute pain and inflammation, as related to selective inhibition of cyclo-oxygenase-2 (COX-2) enzyme and consequent reduction in COX-2-mediated prostanoid mediators. Anti-inflammatory activity of BM might also account for its benefits in cognition.

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Preliminary Assessment of the Anti-Inflammatory Activity of New Structural Honokiol Analogs with a 4′-O-(2-fluoroethyl) Moiety and the Potential of Their 18F-Labeled Derivatives for Neuroinflammation Imaging

Molecules ◽

10.3390/molecules26216630 ◽

2021 ◽

Vol 26 (21) ◽

pp. 6630

Author(s):

Daria D. Vaulina ◽

Kira I. Stosman ◽

Konstantin V. Sivak ◽

Andrey G. Aleksandrov ◽

Nikolai B. Viktorov ◽

...

Keyword(s):

Ex Vivo ◽

Inflammatory Activity ◽

Preliminary Evaluation ◽

Moderate Increase ◽

Biodistribution Studies ◽

Cox 2 ◽

Anti Inflammatory ◽

The Brain

Neolignans honokiol and 4′-O-methylhonokiol (MH) and their derivatives have pronounced anti-inflammatory activity, as evidenced by numerous pharmacological studies. Literature data suggested that cyclooxygenase type 2 (COX-2) may be a target for these compounds in vitro and in vivo. Recent studies of [11C]MPbP (4′-[11С]methoxy-5-propyl-1,1′-biphenyl-2-ol) biodistribution in LPS (lipopolysaccharide)-treated rats have confirmed the high potential of MH derivatives for imaging neuroinflammation. Here, we report the synthesis of four structural analogs of honokiol, of which 4′-(2-fluoroethoxy)-2-hydroxy-5-propyl-1, 1′-biphenyl (F-IV) was selected for labeling with fluorine-18 (T1/2 = 109.8 min) due to its high anti-inflammatory activity confirmed by enzyme immunoassays (EIA) and neuromorphological studies. The high inhibitory potency of F-IV to COX-2 and its moderate lipophilicity and chemical stability are favorable factors for the preliminary evaluation of the radioligand [18F]F-IV in a rodent model of neuroinflammation. [18F]F-IV was prepared with good radiochemical yield and high molar activity and radiochemical purity by 18F-fluoroethylation of the precursor with Boc-protecting group (15) with [18F]2-fluoro-1-bromoethane ([18F]FEB). Ex vivo biodistribution studies revealed a small to moderate increase in radioligand uptake in the brain and peripheral organs of LPS-induced rats compared to control animals. Pretreatment with celecoxib resulted in significant blocking of radioactivity uptake in the brain (pons and medulla), heart, lungs, and kidneys, indicating that [18F]F-IV is likely to specifically bind to COX-2 in a rat model of neuroinflammation. However, in comparison with [11C]MPbP, the new radioligand showed decreased brain uptake in LPS rats and high retention in the blood pool, which apparently could be explained by its high plasma protein binding. We believe that the structure of [18F]F-IV can be optimized by replacing the substituents in the biphenyl core to eliminate these disadvantages and develop new radioligands for imaging activated microglia.

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Design and Synthesis of 2-Mercapto Benzoxazole coupled Benzyl Triazoles as Anti-inflammatory Agents Targeting COX-2 Enzyme

Asian Journal of Chemistry ◽

10.14233/ajchem.2020.22956 ◽

2020 ◽

Vol 32 (12) ◽

pp. 3209-3218

Author(s):

K. Praveen Kumar ◽

Y. Prashanthi ◽

G. Rambabu ◽

Md. Ataur Rahman ◽

J.S. Yadav

Keyword(s):

Chemical Space ◽

Biological Evaluation ◽

Inflammatory Activity ◽

Design Synthesis ◽

Standard Drug ◽

Design And Synthesis ◽

Cox 2 ◽

Anti Inflammatory

In this study, we report the design, synthesis and the biological evaluation of 19 analogues of 2-mercapto benzoxazole coupled benzyl triazoles (BOTs) based on analysis of the binding site and literature of chemical space. These BOTs were evaluated both in vitro and in vivo for their anti-inflammatory activity. Eleven compounds showed less than 10 μM in vitro COX-2 enzyme activities. The most potent analogue among the BOT analogues were BOT15, BOT3 and BOT19 with IC50 3.40 μM, 4.50 μM and 4.57 μM respectively against COX-2. The in vivo anti-inflammatory activity of two BOTs has significantly higher than that of standard drug, ibuprofen. 2-Mercapto benzoxazole coupled benzyl triazoles (BOTs) were also tested for their antioxidant capacity and proved to be an as active scavenger, better than ascorbic acid.

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Design, Synthesis, Antioxidant, Anti-inflammatory Activity and Molecular Docking Studies of Novel 3,4,5-Trisubstituted-1,2,4-Triazole Derivatives Bearing Benzimidazole Moiety

Letters in Organic Chemistry ◽

10.2174/1570178617999201014164403 ◽

2020 ◽

Vol 17 ◽

Author(s):

Ramamurthy Katikireddy ◽

Ramu Kakkerla ◽

M.P.S. Murali Krishna ◽

Gandamalla Durgaiah ◽

Narasimha Reddy Yellu

Keyword(s):

Molecular Docking ◽

Docking Studies ◽

Biological Data ◽

Inflammatory Activity ◽

Design Synthesis ◽

Molecular Docking Studies ◽

Cox 2 ◽

Anti Inflammatory

: 5-(7-Methyl-2-propyl-1H-benzo[d]imidazol-5-yl)-4-phenyl-4H-1,2,4-triazole-3-thiols(6a-i) have been synthesized from key intermediate 7-methyl-2-propyl-1H-benzo[d]imidazole-5-carbohydrazide(3). The hydrazide was treated with different aryl isothiocyanatesto give corresponding thiosemicarbazone derivatives, which underwent cyclization in 4N sodium hydroxide to affordcorresponding title compound. All the compounds evaluated for their in vitro antioxidant and in vivo anti-inflammatory activity. From the results, compounds 6b and 6e have shown potential antioxidant and anti-inflammatory activity. The biological data was further supported by molecular docking studies, which revealed the binding pattern and the affinity of the molecules in the active site of COX-2.

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