scholarly journals Thymus algeriensis and Thymus fontanesii: Chemical Composition, In Vivo Antiinflammatory, Pain Killing and Antipyretic Activities: A Comprehensive Comparison

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 599 ◽  
Author(s):  
Mansour Sobeh ◽  
Samar Rezq ◽  
Mohammed Cheurfa ◽  
Mohamed A.O. Abdelfattah ◽  
Rasha M.H. Rashied ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Secondary Metabolites ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Thymus Algeriensis ◽  
Comprehensive Comparison ◽  
Cox 2 ◽  
Anti Inflammatory

This study aimed to investigate the chemical composition, and evaluate the antioxidant, anti-inflammatory, anti-pyretic, and the analgesic properties of methanol extracts from the leaves of Thymus algeriensis and Thymus fontanesii (Lamiaceae). Thirty-five secondary metabolites were characterized in both extracts using HPLC-PDA-ESI-MS/MS. Phenolic acids, mainly rosmarinic acid and its derivatives, dominated the T. algeriensis extract, while the phenolic diterpene carnosol and the methylated flavonoid salvigenin, prevailed in T. fontanesii extract. Molecular docking study was carried out to estimate the anti-inflammatory potential and the binding affinities of some individual secondary metabolites from both extracts to the main enzymes involved in the inflammation pathway. In vitro enzyme inhibitory assays and in vivo assays were used to investigate the antioxidant and anti-inflammatory activities of the extracts. Results revealed that both studied Thymus species exhibited antioxidant, anti-inflammatory, analgesic, and antipyretic effects. They showed to be a more potent antioxidant than ascorbic acid and more selective against cyclooxygenase (COX-2) than diclofenac and indomethacin. Relatively, the T. fontanesii extract was more potent as COX-2 inhibitor than T. algeriensis. In conclusion, Thymus algeriensis and Thymus fontanesii may be interesting candidates for the treatment of inflammation and oxidative stress-related disorders.

Synthesis of new hexahydropyrimido[1,2-a]azepine derivatives bearing functionalized aryl and heterocyclic moieties as anti-inflammatory agents

2021 ◽  
Author(s):  
Hassanein H Hassanein ◽  
Doaa E Abdel Rahman ◽  
Marwa A Fouad ◽  
Rehab F Ahmed
Keyword(s):  
Molecular Docking ◽  
Binding Sites ◽  
Docking Study ◽  
In Vivo Studies ◽  
Molecular Docking Study ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

New hexahydropyrimido[1,2- a]azepine derivatives bearing functionalized aryl and heterocyclic moieties were synthesized as anti-inflammatory agents with better safety profiles. All synthesized compounds were assessed in vitro for their COX-1 and COX-2 inhibition activities. The most selective compounds, 2f, 5 and 6, were further evaluated for their in vivo anti-inflammatory activity and PGE2 inhibitory activity. To rationalize their selectivity, molecular docking within COX-1 and COX-2 binding sites was performed. Their physicochemical properties and drug-like nature profile were also calculated. The good activity and selectivity of compounds 2f, 5 and 6 were rationalized using a molecular docking study and supported by in vivo studies. These promising findings are encouraging for performing future investigations of these derivatives.

scholarly journals Molecular Docking Study of 3, 4- Dihydropyrimidone Derivatives as Novel Anti-inflammatory Agents

2021 ◽  
pp. 481-487
Author(s):  
Amit N. Panaskar ◽  
Ashish Jain ◽  
Pradeep Kumar Mohanty
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Docking Study ◽  
Protein Data Bank Code ◽  
Molecular Docking Study ◽  
Docking Score ◽  
Enzyme Active Site ◽  
Cox 2 ◽  
Anti Inflammatory

Aim: Currently, researchers have developed a lot of new active substances as anti-inflammatory agents. One of the target proteins for anti-inflammatory agents is the selective COX-2 active site. Selective COX-2 inhibition is the regulator of the inflammatory reaction cascade. In this research, 3, 4- Dihydropyrimidone derivatives were used to design the anti-inflammatory agent through a selective COX-2 inhibition. The potential activity of 3, 4- Dihydropyrimidone derivatives maybe increase due to the preparation of the Schiff base with aromatic aldehydes. Selective COX-2 inhibition was required to predict their anti-inflammatory activity so, the aim in the present study, molecular docking study of 3,4- dihydropyrimidone derivatives have performed using COX-2 enzyme active site. Methodology: The molecular docking of 3, 4-dihydropyrimidone derivatives were carried out using AutoDock vina Ver.1.1.2. Twenty 3,4-dihydropyrimidone derivatives were docked into the COX-2 active site with Protein data bank code 3LN1. The interactions were evaluated based on the docking score. Celecoxib was used as the reference standard for this study. Results: Twenty 3, 4- dihydropyrimidone derivatives showed the approximate docking score -8.4 to -10.1 kcal/mol. Fourteen 3,4-dihydropyrimidone derivatives have a greater docking score compared to celecoxib used as a standard compound. Derivative D-1 had higher binding energy than other 3,4-dihydropyrimidone derivatives because it has the smallest docking score. Conclusion: All new 3,4-dihydropyrimidone derivatives are feasible to synthesize and performed their in-vitro evaluation.

scholarly journals Alantolactone, a natural sesquiterpene lactone, has potent antitumor activity against glioblastoma by targeting IKKβ kinase activity and interrupting NF-κB/COX-2-mediated signaling cascades

2017 ◽  
Vol 36 (1) ◽  
Author(s):  
Xun Wang ◽  
Zhenlong Yu ◽  
Chao Wang ◽  
Wei Cheng ◽  
Xiangge Tian ◽  
...  
Keyword(s):  
Kinase Activity ◽  
Treatment Strategies ◽  
Docking Study ◽  
Signaling Cascades ◽  
Quantitative Detection ◽  
Molecular Docking Study ◽  
Wide Range ◽  
Cox 2

Abstract Background Glioblastoma multiforme (GBM) is one of the most refractory and palindromic central nervous system (CNS) neoplasms, and current treatments have poor effects in GBM patients. Hence, the identification of novel therapeutic targets and the development of effective treatment strategies are essential. Alantolactone (ATL) has a wide range of pharmacological activities, and its anti-tumor effect is receiving increasing attention. However, the molecular mechanism underlying the anti-GBM activity of ATL remains poorly understood. Methods The biological functions of ATL in GBM cells were investigated using migration/invasion, colony formation and cell cycle/apoptosis assays. The localization of nuclear factor kappa B (NF-κB) p50/p65 and its binding to the cyclooxygenase 2 (COX-2) promoter were determined using confocal immunofluorescence, a streptavidin-agarose pulldown assay and a chromatin immunoprecipitation (ChIP) assay. IKKβ kinase activity was determined using a cell IKKβ kinase activity spectrophotometry quantitative detection kit and a molecular docking study. LC-MS/MS analysis was performed to determine the ability of ATL to traverse the blood-brain barrier (BBB). The in vivo anti-tumor efficacy of ATL was also analyzed in xenografted nude mice. Western blot analysis was performed to detect the protein expression levels. Results ATL significantly suppressed the growth of GBM in vivo and in vitro. ATL significantly reduced the expression of COX-2 by inhibiting the kinase activity of IKKβ by targeting the ATP-binding site and then attenuating the binding of NF-κB to the COX-2 promoter region. Furthermore, ATL induced apoptosis by activating the cytochrome c (cyt c)/caspase cascade signaling pathway. Moreover, ATL could penetrate the BBB. Conclusions ATL exerts its anti-tumor effects in human GBM cells at least in part via NF-κB/COX-2-mediated signaling cascades by inhibiting IKKβ kinase activity. ATL, which is a natural small molecule inhibitor, is a promising candidate for clinical applications in the treatment of CNS tumors.

scholarly journals Synthesis, Anti-Inflammatory Activity, and In Silico Study of Novel Diclofenac and Isatin Conjugates

2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Musab Mohamed Ibrahim ◽  
Tilal Elsaman ◽  
Mosab Yahya Al-Nour
Keyword(s):  
Virtual Screening ◽  
Condensation Reaction ◽  
Docking Study ◽  
Positive Control ◽  
Inflammatory Activity ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Chemical Structures ◽  
Anti Inflammatory

The design, synthesis, and development of novel non-steroidal anti-inflammatory drugs (NSAIDs) with better activity and lower side effects are respectable area of research. Novel Diclofenac Schiff’s bases (M1, M2, M4, M7, and M8) were designed and synthesized, and their respective chemical structures were deduced using various spectral tools (IR, 1H NMR, 13C NMR, and MS). The compounds were synthesized via Schiff’s condensation reaction and their anti-inflammatory activity was investigated applying the Carrageenan-induced paw edema model against Diclofenac as positive control. Percentage inhibition of edema indicated that all compounds were exhibiting a comparable anti-inflammatory activity as Diclofenac. Moreover, the anti-inflammatory activity was supported via virtual screening using molecular docking study. Interestingly compound M2 showed the highest in vivo activity (61.32% inhibition) when compared to standard Diclofenac (51.36% inhibition) as well as the best binding energy score (-10.765) and the virtual screening docking score (-12.142).

2,5-disubstituted-4-thiazolidinones: Synthesis, anti-inflammatory, free radical scavenging potentials and structural insights through molecular docking

2021 ◽  
Vol 18 ◽  
Author(s):  
Jagseer Singh ◽  
Pooja A Chawla ◽  
Rohit Bhatia ◽  
Shamsher Singh
Keyword(s):  
Free Radicals ◽  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Assay Method ◽  
Acidic Group ◽  
Active Compounds ◽  
Cox 2 ◽  
Anti Inflammatory

: The present work reports synthesis and screening of fifteen 2,5-disubstituted-4-thiazolidinones with different substitutions of varied arylidene groups at imino. The structures of the compounds were confirmed by spectral characterization. The compounds were subjected to in vivo anti-inflammatory and in vitro antioxidant activities. The derivatives possessed remarkable activities quite close to standard drugs used. Unlike conventional non-selective NSAIDs, the synthesized compounds did not contain any acidic group, thereby ensuring a complete cure from ulcers. To further substantiate the claim for safer derivatives, the active compounds were docked against the cyclooxygenase (COX)-2 enzyme. It was found that 4-fluorophenylimino substituent at 2- position and 3-nitro moiety on a 5-benzylidene nucleus of the 4-thiazolidinone derivative fitted in the COX-2 binding pocket. The compounds exhibited remarkable activity in scavenging free radicals, as depicted by the DPPH assay method. The structure-activity relationship was also established in the present work with respect to the nature and position of the substituents. The active compounds were evaluated for drug-like nature under Lipinski’s rule of five, and the toxicity behaviour of active compounds was predicted using ADMETlab software. The compounds have the potential to target degenerative disorders associated with inflammation and the generation of free radicals.

scholarly journals Rationally synthesized coumarin based pyrazolines ameliorate carrageenan induced inflammation through COX-2/pro-inflammatory cytokine inhibition

MedChemComm ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 421-430 ◽  
Author(s):  
Priyanka Chandel ◽  
Anoop Kumar ◽  
Nishu Singla ◽  
Anshul Kumar ◽  
Gagandeep Singh ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Cytokine Inhibition ◽  
Cox 2 ◽  
Anti Inflammatory

In the present work, coumarin based pyrazolines (7a–g) have been synthesized and investigated for their in vitro and in vivo anti-inflammatory potential.

scholarly journals Nerolidol Mitigates Colonic Inflammation: An Experimental Study Using both In Vivo and In Vitro Models

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2032
Author(s):  
Vishnu Raj ◽  
Balaji Venkataraman ◽  
Saeeda Almarzooqi ◽  
Sanjana Chandran ◽  
Shreesh K. Ojha ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
In Vitro Models ◽  
Mrna Levels ◽  
Colonic Inflammation ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Ht 29

Nerolidol (NED) is a naturally occurring sesquiterpene alcohol present in various plants with potent anti-inflammatory effects. In the current study, we investigated NED as a putative anti-inflammatory compound in an experimental model of colonic inflammation. C57BL/6J male black mice (C57BL/6J) were administered 3% dextran sodium sulfate (DSS) in drinking water for 7 days to induce colitis. Six groups received either vehicle alone or DSS alone or DSS with oral NED (50, 100, and 150 mg/kg body weight/day by oral gavage) or DSS with sulfasalazine. Disease activity index (DAI), colonic histology, and biochemical parameters were measured. TNF-α-treated HT-29 cells were used as in vitro model of colonic inflammation to study NED (25 µM and 50 µM). NED significantly decreased the DAI and reduced the inflammation-associated changes in colon length as well as macroscopic and microscopic architecture of the colon. Changes in tissue Myeloperoxidase (MPO) concentrations, neutrophil and macrophage mRNA expression (CXCL2 and CCL2), and proinflammatory cytokine content (IL-1β, IL-6, and TNF-α) both at the protein and mRNA level were significantly reduced by NED. The increase in content of the proinflammatory enzymes, COX-2 and iNOS induced by DSS were also significantly inhibited by NED along with tissue nitrate levels. NED promoted Nrf2 nuclear translocation dose dependently. NED significantly increased antioxidant enzymes activity (Superoxide dismutase (SOD) and Catalase (CAT)), Hemeoxygenase-1 (HO-1), and SOD3 mRNA levels. NED treatment in TNF-α-challenged HT-29 cells significantly decreased proinflammatory chemokines (CXCL1, IL-8, CCL2) and COX-2 mRNA levels. NED supplementation attenuates colon inflammation through its potent antioxidant and anti-inflammatory activity both in in vivo and in vitro models of colonic inflammation.

Synthesis of new ibuprofen hybrid conjugates as potential anti-inflammatory and analgesic agents

2020 ◽  
Vol 12 (15) ◽  
pp. 1369-1386
Author(s):  
Siva S Panda ◽  
Adel S Girgis ◽  
Hitesh H Honkanadavar ◽  
Riham F George ◽  
Aladdin M Srour
Keyword(s):  
Writhing Test ◽  
Rat Paw Edema ◽  
Analgesic Agents ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Rat Paw ◽  
Inhibition Studies

Background: A new set of hybrid conjugates derived from 2-(4-isobutylphenyl)propanoic acid (ibuprofen) is synthesized to overcome the drawbacks of the current non-steroidal anti-inflammatory drugs. Results & methodology: Synthesized conjugates were screened for their anti-inflammatory, analgesic and ulcerogenic properties. Few conjugates were found to have significant anti-inflammatory properties in the carrageenan-induced rat paw edema test, while a fair number of conjugates showed promising peripheral analgesic activity in the acetic acid-induced writhing test as well as central analgesic properties in the in vivo hot plate technique. The newly synthesized conjugates did not display any ulcerogenic liability. Conclusion: In vitro, COX-1 and COX-2 enzyme inhibition studies raveled compound 7e is more selective toward COX-2 compared with ibuprofen.

scholarly journals In Vitro and In Silico Evaluation of Anticancer Activity of New Indole-Based 1,3,4-Oxadiazoles as EGFR and COX-2 Inhibitors

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5190
Author(s):  
Belgin Sever ◽  
Mehlika Dilek Altıntop ◽  
Ahmet Özdemir ◽  
Gülşen Akalın Çiftçi ◽  
Doha E. Ellakwa ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Growth Factor Receptor ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Egfr Inhibition ◽  
Cancer Management ◽  
Cox 2 ◽  
Cox 2 Inhibitors

Epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) are crucial targetable enzymes in cancer management. Therefore, herein, new 2-[(5-((1H-indol-3-yl)methyl)-1,3,4-oxadiazol-2-yl)thio]-N-(thiazol/benzothiazol-2-yl)acetamides (2a–i) were designed and synthesized as EGFR and COX-2 inhibitors. The cytotoxic effects of compounds 2a–i on HCT116 human colorectal carcinoma, A549 human lung adenocarcinoma, and A375 human melanoma cell lines were determined using MTT assay. 2-[(5-((1H-Indol-3-yl)methyl)-1,3,4-oxadiazol-2-yl)thio]-N-(6-ethoxybenzothiazol-2-yl)acetamide (2e) exhibited the most significant anticancer activity against HCT116, A549, and A375 cell lines with IC50 values of 6.43 ± 0.72 μM, 9.62 ± 1.14 μM, and 8.07 ± 1.36 μM, respectively, when compared with erlotinib (IC50 = 17.86 ± 3.22 μM, 19.41 ± 2.38 μM, and 23.81 ± 4.17 μM, respectively). Further mechanistic assays demonstrated that compound 2e enhanced apoptosis (28.35%) in HCT116 cells more significantly than erlotinib (7.42%) and caused notable EGFR inhibition with an IC50 value of 2.80 ± 0.52 μM when compared with erlotinib (IC50 = 0.04 ± 0.01 μM). However, compound 2e did not cause any significant COX-2 inhibition, indicating that this compound showed COX-independent anticancer activity. The molecular docking study of compound 2e emphasized that the benzothiazole ring of this compound occupied the allosteric pocket in the EGFR active site. In conclusion, compound 2e is a promising EGFR inhibitor that warrants further clinical investigations.

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