Discovery of a COX-2 selective inhibitor hit with anti-inflammatory activity and gastric ulcer protective effect

2017 ◽  
Vol 9 (16) ◽  
pp. 1899-1912 ◽  
Author(s):  
Mohamed A Abdelgawad ◽  
Rania B Bakr ◽  
Ahmed O El-Gendy ◽  
Gehan M Kamel ◽  
Amany A Azouz ◽  
...  
Keyword(s):  
Gastric Ulcer ◽  
Protective Effect ◽  
Selective Inhibitor ◽  
Inflammatory Activity ◽  
Cox 2 ◽  
Anti Inflammatory

Design, Synthesis, Characterization and in silico molecular docking studies and in vivo anti-inflammatory Activity of Pyrazoline clubbed Thiazolinone Derivatives

2020 ◽  
Vol 17 ◽  
Author(s):  
Deepak Kumar Singh ◽  
Mayank Kulshreshtha ◽  
Yogesh Kumar ◽  
Pooja A Chawla ◽  
Akash Ved ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Biological Activities ◽  
Inflammatory Activity ◽  
Standard Drug ◽  
Docking Score ◽  
Chemical Structures ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Background: The pyrazolines give the reactions of aliphatic derivatives, resembling unsaturated compounds in their behavior towards permanganate and nascent hydrogen. This nucleus has been associated with various biological activities including inflammatory. Thiazolinone is a heterocyclic compound that contains both sulfur and nitrogen atom with a carbonyl group in their structure.Thiazolinone and their derivatives have attracted continuing interest because of their various biological activities, such as anti-inflammatory, antimicrobial, anti-proliferative, antiviral, anticonvulsant etc. The aim of the research was to club pyrazoline nucleus with thiazolinone in order to have significantanti-inflammatory activity. The synthesized compounds were chemically characterized for the establishment of their chemical structures and to evaluate as anti-inflammatory agent. Method: In the present work, eight derivatives of substituted pyrazoline (PT1-PT8) were synthesized by a three step reaction.The compounds were subjected to spectral analysis by Infrared, Mass and Nuclear magnetic resonance spectroscopy and elemental analysis data. All the synthesized were evaluated for their in vivo anti-inflammatory activity. The synthesized derivatives were evaluated for their affinity towards target COX-1 and COX-2, using indomethacin as the reference compound molecular docking visualization through AutoDock Vina. Results: Compounds PT-1, PT-3, PT-4 and PT-8 exhibited significant anti-inflammatory activity at 3rd hour being 50.7%, 54.3%, 52.3% and 57% respectively closer to that of the standard drug indomethacin (61.9%).From selected anti-inflammatory targets, the synthesized derivatives exhibited better interaction with COX-1 and COX-2 receptor, where indomethacin showed docking score of -6.5 kJ/mol, compound PT-1 exhibited highest docking score of -9.1 kJ/mol for COX-1 and compound PT-8 having docking score of 9.4 kJ/mol for COX-2. Conclusion: It was concluded that synthesized derivatives have more interaction with COX-2 receptors in comparison to the COX-1 receptors because the docking score with COX-2 receptors were very good. It is concluded that the synthesized derivatives (PT-1 to PT-8) are potent COX-2 inhibitors.

scholarly journals Evaluation of Anticonvulsant Activity of Dual COX-2/5-LOX Inhibitor Darbufelon and Its Novel Analogues

2021 ◽  
Vol 89 (2) ◽  
pp. 22
Author(s):  
Mariia Mishchenko ◽  
Sergiy Shtrygol’ ◽  
Andrii Lozynskyi ◽  
Semen Khomyak ◽  
Volodymyr Novikov ◽  
...  
Keyword(s):  
Drug Design ◽  
Anticonvulsant Activity ◽  
Inflammatory Activity ◽  
Significant Protection ◽  
Protection Level ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Target Agent

Neuroinflammation is an integral part of epilepsy pathogenesis and other convulsive conditions, and non-steroidal anti-inflammatory drugs (NSAIDs) present a potent tool for the contemporary search and design of novel anticonvulsants. In the present paper, evaluation of the anticonvulsant activity of the potential NSAID dual COX-2/5-LOX inhibitor darbufelone methanesulfonate using an scPTZ model in mice in dose 100 mg/kg is reported. Darbufelone possesses anticonvulsant properties in the scPTZ model and presents interest for in-depth studies as a possible anticonvulsant multi-target agent with anti-inflammatory activity. The series of 4-thiazolidinone derivatives have been synthesized following the analogue-based drug design and hybrid-pharmacophore approach using a darbufelone matrix. The synthesized derivatives showed a significant protection level for animals in the scPTZ model and are promising compounds for the design of potential anticonvulsants with satisfactory drug-like parameters.

scholarly journals ANTI-INFLAMMATORY ACTIVITY OF CURCUMIN AND CAPSAICIN AUGMENTED IN COMBINATION

2017 ◽  
Vol 9 (6) ◽  
pp. 145
Author(s):  
Thriveni Vasanth Kumar ◽  
Manjunatha H. ◽  
Rajesh Kp
Keyword(s):  
Acetic Acid ◽  
Protective Effect ◽  
Vascular Permeability ◽  
Diclofenac Sodium ◽  
Significant Inhibition ◽  
Inflammatory Activity ◽  
Anti Inflammatory ◽  
The Individual

Objective: Dietary curcumin and capsaicin are well known for their health beneficial potencies. The current study was done to assess the anti-inflammatory activity of curcumin, capsaicin and their combination by employing in vitro and in vivo models.Methods: We investigated the protective effect of curcumin, capsaicin and their combination using in vitro heat induced human red blood cell (HRBC) membrane stabilisation, in vivo 3% agar induced leukocyte mobilisation and acetic acid induced vascular permeability assay.Results: Curcumin, capsaicin and their combination exhibited concentration dependent protective effect against heat-induced HRBC membrane destabilisation, while combined curcumin and capsaicin restored 87.0±0.64 % membrane stability and it is found to be better than curcumin, capsaicin and diclofenac sodium (75.0±0.25. 72±0.9 and 80.0±0.31 %) protective effect. In agar suspension induced leukocyte mobilization assay, the combined curcumin and capsaicin had shown 39.5±1.58 % of inhibition compared to individual curcumin and capsaicin, which showed moderate inhibition of 16.0±3.14 and 21.6±2.17 % respectively. Besides, the combined curcumin and capsaicin had shown highly significant inhibition of acetic acid-induced vascular permeability in rats (62.0±3.14 %), whereas individual curcumin and capsaicin showed moderate inhibition of vascular permeability with 36.0±2.41 and 43.0±1.92 % respectively.Conclusion: This study demonstrates the significant anti-inflammatory property of combined curcumin and capsaicin at half of the individual concentration of curcumin and capsaicin.

Non-acidic 1,3,4-trisubstituted-pyrazole derivatives as lonazolac analogs with promising COX-2 selectivity, anti-inflammatory activity and gastric safety profile

2018 ◽  
Vol 77 ◽  
pp. 568-578 ◽  
Author(s):  
Khaled R.A. Abdellatif ◽  
Wael A.A. Fadaly ◽  
Yaseen A.M.M. Elshaier ◽  
Waleed A.M. Ali ◽  
Gehan M. Kamel
Keyword(s):  
Safety Profile ◽  
Inflammatory Activity ◽  
Pyrazole Derivatives ◽  
Cox 2 ◽  
Anti Inflammatory

An Overview of Novel Bioactive Compounds with Potent Anti-Inflammatory Activity via Dual COX-2 and 5-LOX Enzyme Inhibition

2021 ◽  
Vol 18 ◽  
Author(s):  
Roopal Mittal ◽  
Shailesh Sharma ◽  
Ajay Singh Kushwah
Keyword(s):  
Bioactive Compounds ◽  
Enzyme Inhibitors ◽  
World Health Organisation ◽  
The Body ◽  
Inflammatory Activity ◽  
World Health ◽  
Quality Data ◽  
The World ◽  
Cox 2 ◽  
Anti Inflammatory

Background: Inflammation is the earliest body defence mechanism in which the immune system recognises and counters the antigens and aids in healing the disease. The World Health Organisation suggests that inflammation is one of the greatest causes of death in the world. Inflammation could be acute or chronic due to the release of inflammatory mediators i.e. prostaglandins, leukotrienes due to mitogens, antigens or cytokines found in the body. Methods: Bibliographic database using pub med cites for peer-reviewed research articles with titles containing dual COX-2 and 5-LOX enzyme inhibitors, heterocyclic moieties, with AND Boolean operator's terms since last ten years of literature work. The quality papers containing the natural or synthetic lead compounds were extracted; the detailed study and conceptual framework attracted its attention. Results: Out of 127 research and review articles evaluated, 54 articles were cited to provide high quality data regarding pharmacoactive molecules having anti-inflammatory activity via dual COX-2/5-LOX inhibition. In addition, highlighting their in silico and experimental wet laboratory studies in increasing order over the past decade with the best illustration of dual enzyme inhibitory activity. Conclusion: This review gathered details of isolated bioactive compounds such as pyrazole, coumaperine, indoles, phenanthrene derivatives that have been significantly reported for anti-inflammatory activities.

scholarly journals IN SILICO DESIGN AND MOLECULAR DOCKING STUDIES OF SOME 1, 2-BENZISOXAZOLE DERIVATIVES FOR THEIR ANALGESIC AND ANTI-INFLAMMATORY ACTIVITY

2017 ◽  
Vol 9 (3) ◽  
pp. 133
Author(s):  
Sarath Sasi Kumar ◽  
Anjali T
Keyword(s):  
Molecular Docking ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Analgesic Activity ◽  
In Silico ◽  
Docking Studies ◽  
Inflammatory Activity ◽  
Nicotinic Acetylcholine ◽  
Cox 2 ◽  
Anti Inflammatory

Objective: In silico design and molecular docking of 1,2-benzisoxazole derivatives for their analgesic and anti-inflammatory activity using computational methods.Methods: In silico molecular properties of 1,2-benzisoxazole derivatives were predicted using various software’s such as Chemsketch, Molinspiration, PASS and Schrodinger to select compounds having optimum drug-likeness, molecular descriptors resembling those of standard drugs and not violating the ‘Lipinski rule of 5’. Molecular docking was performed on active site of nicotinic acetylcholine receptor (PDB: 2KSR) for analgesic activity and COX-2 (PDB: 6COX) for anti-inflammatory activity using Schrodinger under maestro molecular modelling environment.Results: From the results of molecular docking studies of 1,2-benzisoxazole derivatives, all the compounds showed good binding interactions with Nicotinic acetylcholine receptor and COX-2. Compounds 4a and 4c showed highest binding scores (-7.46 and-7.21 respectively) with nicotinic acetylcholine receptor and exhibited maximum analgesic activity. Compound 4a showed highest binding score (-7.8) with COX-2 and exhibited maximum anti-inflammatory activity.Conclusion: All the derivatives of 1,2-benzisoxazole showed good analgesic and anti-inflammatory activity as predicted using molecular docking on respective receptors.

Design and synthesis of pyrimidine-5-carbonitrile hybrids as COX-2 inhibitors: Anti-inflammatory activity, ulcerogenic liability, histopathological and docking studies

2020 ◽  
pp. 104555
Author(s):  
Abdallah M. Alfayomy ◽  
Salah A. Abdel-Aziz ◽  
Adel A. Marzouk ◽  
Montaser Sh. A. Shaykoon ◽  
Atsushi Narumi ◽  
...  
Keyword(s):  
Docking Studies ◽  
Inflammatory Activity ◽  
Design And Synthesis ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors

scholarly journals ANTI-INFLAMMATORY ACTIVITY OF BACTERIA ASSOCIATED WITH MARINE SPONGE (HALICLONA AMBOINENSIS) VIA REDUCTING NO PRODUCTION AND INHIBITING CYCLOOXYGENASE-1, CYCLOOXYGENASE-2, AND SECRETORY PHOSPHOLIPASE A2 ACTIVITIES

2017 ◽  
Vol 10 (11) ◽  
pp. 95 ◽  
Author(s):  
Yosie Andriani ◽  
Leni Marlina ◽  
Habsah Mohamad ◽  
Hermansyah Amir ◽  
Siti Aisha M Radzi ◽  
...  
Keyword(s):  
Methanol Extract ◽  
Inflammatory Activity ◽  
No Production ◽  
Secretory Phospholipase A2 ◽  
Phytochemical Screening ◽  
Spla2 Activity ◽  
Cyclooxygenase 1 ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

  Objective: This study aimed to investigate the anti-inflammatory activity of methanol extract and fractions of bacteria associated with sponge (Haliclona amboinensis) and to evaluate their effect in reducing NO production and inhibiting cyclooxygenase-1 (COX-1), cyclooxgenase-2 (COX-2) and secretory phospholipase A2 (sPLA2) activity.Methods: All bacterial isolates were cultured and supernatants were collected for the extraction of secondary metabolites using diaion HP-20 to obtain methanol extracts. Evaluation of cytotoxicity property was carried out on macrophage cell lines (RAW264.7) by 3-(4,5-dimethylthiazol- 2-yl) 2,5-diphenyl tetrazoliumbromide assay. Anti-inflammatory screening was done by inducible nitric oxide assay on RAW264.7 cell lines with lipopolysaccharide (LPS) stimulation. Dianion HP-20 was used to remove salt content. A selected methanol extract was subjected to further fractionations by C-18 reverse phase and their anti-inflammatory potential was evaluated by COX-1 and COX-2, and sPLA2 enzymatic assay.Results: Seven methanol extracts showed no cytotoxic property against RAW 264.7 cell line (inhibitory concentration 50% > 30 μg/ml) and selected for anti-inflammatory screening assay. Result showed methanol extract HM 1.2 reduced NO production >80% and it has been selected for phytochemical screening, further fractionations and assay. Phytochemical screening showed alkaloids and terpenoids present in the HM 1.2. The HM 1.2 and its fractions (F1, F2, F1C1, F1C2, F1C3, and F1C4) were proven to inhibit COX-1, COX-2, and sPLA2 activity in the range of 60.516-116.886%, 20.554- 116.457%, and 70.2667-114.8148%, respectively.Conclusions: This study revealed that bacteria associated with H. amboinensis have produced anti-inflammatory activity via reducing NO production and inhibiting COX-1, COX-2, and sPLA2 activity. 

scholarly journals Anti-Inflammatory Activity of the Active Compounds of Sanguisorbae Radix In Macrophages and in Vivo Toxicity Evaluation in Zebrafish

Cosmetics ◽  
2019 ◽  
Vol 6 (4) ◽  
pp. 68
Author(s):  
Young-Ah Jang ◽  
Yong Hur ◽  
Jin-Tae Lee
Keyword(s):  
Target Genes ◽  
Inflammatory Activity ◽  
Dependent Manner ◽  
Active Components ◽  
Necrosis Factor Alpha ◽  
In Vivo Toxicity ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Sanguisorbae Radix

Sanguisorbae Radix (SR) is the root of the Sanguisorba officinalis L., a plant native to Asian countries and used in traditional medicine. We isolated the active components of SR and investigated their anti-inflammatory potential. Quercetin (QC), (+)-catechin (CC), and gallic acid (GA) were isolated from acetone extracts of SR. To elucidate the molecular mechanism by which these compounds suppress inflammation, we analyzed the transcriptional up-regulation of inflammatory mediators, such as nuclear factor-kappa B (NF-κB) and its target genes, inducible NOS (iNOS), and cyclooxygenase (COX)-2, in lipopolysaccharide (LPS)-stimulated macrophage RAW264.7 cells. Notably, QC, CC, and GA were found to inhibit the production of nitric oxide, tumor necrosis factor-alpha, and prostaglandin in a dose-dependent manner. Western blot results indicate that the compounds decreased the expression of iNOS and COX-2 proteins. Furthermore, the compounds decreased phosphorylation of IKK, IκB, ERK, p-38, and JNK proteins in LPS-induced cells. The results support the notion that QC, CC, and GA can potently inhibit the inflammatory response, with QC showing the highest anti-inflammatory activity. In in vivo toxicity studies in zebrafish (Danio rerio), QC showed no toxicity up to 25 μg/mL. Therefore, QC has non-toxic potential as a skin anti-inflammatory biomaterial.

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