Synthesize of New Ibuprofen and Naproxen Sulphonamide Conjugate with Anti-Inflammatory Study and Molecular Docking Study

2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Tagreed N-A Omar ◽  
Monther F Mahdi ◽  
May Mohammed Jawad Al-Mudhafar ◽  
ZainabBassim .
Keyword(s):  
Pharmacological Study ◽  
Docking Study ◽  
Synthetic Approach ◽  
Molecular Docking Study ◽  
Nmr Data ◽  
Ft Ir ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Gastric Irritation

Non-steroidal anti-inflammatory drugs (NSAIDs) contain free –COOH which thought to be responsible for the GI irritation associated with all traditional NSAIDs. The esterification of this group is one of an approach to ultimate aim for reduce the gastric irritation; so in this study we synthesized and preliminarily evaluated new ester compounds as new analogues with expected selectivity toward COX-2 enzyme. Synthetic procedures have been successfully developed for the generation of the target compounds (III a and b). The synthetic approach involved multi-steps procedures which include: Synthesis of 4-hydroxy benzene sulphonamide ( I b ), synthesis of Naproxen and Ibuprofen acyl chloride and then reacting them with 4-hydroxy benzene sulphonamide to form final compounds ( III a-b) .The structures of these compounds were identified and characterized using (TLC), infrared spectroscopy (FT-IR), 1H NMR data and microanalysis (CHN). Pharmacological study as anti-inflammatory activities for the final compounds were studied in rats by induced edema type of inflammation. Moreover, the results of a docking study of compounds III a-b into the COX-2 binding site revealed that its mechanism was possibly similar to that of naproxen, a COX-2 inhibitor. The effect of them on COX-2 antibody was showed it could significantly inhibit COX-2 activity.

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.

Identification of natural compounds with analgesic and anti-inflammatory properties using machine learning and molecular docking studies

2021 ◽  
Vol 18 ◽  
Author(s):  
Mohammad Firoz Khan ◽  
Ridwan Bin Rashid ◽  
Mohammad A. Rashid
Keyword(s):  
Machine Learning ◽  
Natural Products ◽  
Molecular Docking ◽  
High Throughput ◽  
In Silico ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Natural Sources ◽  
Cox 2 ◽  
Anti Inflammatory

Background: Natural products have been a rich source of compounds for drug discovery. Usually, compounds obtained from natural sources have little or no side effects, thus searching for new lead compounds from traditionally used plant species is still a rational strategy. Introduction: Natural products serve as a useful repository of compounds for new drugs; however, their use has been decreasing, in part because of technical barriers to screening natural products in high-throughput assays against molecular targets. To address this unmet demand, we have developed and validated a high throughput in silico machine learning screening method to identify potential compounds from natural sources. Methods: In the current study, three machine learning approaches, including Support Vector Machine (SVM), Random Forest (RF) and Gradient Boosting Machine (GBM) have been applied to develop the classification model. The model was generated using the cyclooxygenase-2 (COX-2) inhibitors reported in the ChEMBL database. The developed model was validated by evaluating the accuracy, sensitivity, specificity, Matthews correlation coefficient and Cohen’s kappa statistic of the test set. The molecular docking study was conducted on AutoDock vina and the results were analyzed in PyMOL. Results: The accuracy of the model for SVM, RF and GBM was found to be 75.40 %, 74.97 % and 74.60 %, respectively which indicates the good performance of the developed model. Further, the model has demonstrated good sensitivity (61.25 % - 68.60 %) and excellent specificity (77.72 %- 81.41 %). Application of the model on the NuBBE database, a repository of natural compounds, led us to identify a natural compound, enhydrin possessing analgesic and anti-inflammatory activities. The ML methods and the molecular docking study suggest that enhydrin likely demonstrates its analgesic and anti-inflammatory actions by inhibiting COX-2. Conclusion: Our developed and validated in silico high throughput ML screening methods may assist in identifying drug-like compounds from natural sources.

scholarly journals New 1,3,4-Oxadiazole Derivatives of Pyridothiazine-1,1-Dioxide with Anti-Inflammatory Activity

2020 ◽  
Vol 21 (23) ◽  
pp. 9122
Author(s):  
Teresa Glomb ◽  
Benita Wiatrak ◽  
Katarzyna Gębczak ◽  
Tomasz Gębarowski ◽  
Dorota Bodetko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Docking Study ◽  
Dermal Fibroblasts ◽  
Inflammatory Activity ◽  
Molecular Docking Study ◽  
Screening Assay ◽  
Binding Interaction ◽  
Cox Inhibitor ◽  
Cox 2 ◽  
Anti Inflammatory

Numerous studies have confirmed the coexistence of oxidative stress and inflammatory processes. Long-term inflammation and oxidative stress may significantly affect the initiation of the neoplastic transformation process. Here, we describe the synthesis of a new series of Mannich base-type hybrid compounds containing an arylpiperazine residue, 1,3,4-oxadiazole ring, and pyridothiazine-1,1-dioxide core. The synthesis was carried out with the hope that the hybridization of different pharmacophoric molecules would result in a synergistic effect on their anti-inflammatory activity, especially the ability to inhibit cyclooxygenase. The obtained compounds were investigated in terms of their potencies to inhibit cyclooxygenase COX-1 and COX-2 enzymes with the use of the colorimetric inhibitor screening assay. Their antioxidant and cytotoxic effect on normal human dermal fibroblasts (NHDF) was also studied. Strong COX-2 inhibitory activity was observed after the use of TG6 and, especially, TG4. The TG11 compound, as well as reference meloxicam, turned out to be a preferential COX-2 inhibitor. TG12 was, in turn, a non-selective COX inhibitor. A molecular docking study was performed to understand the binding interaction of compounds at the active site of cyclooxygenases.

scholarly journals Computational analysis of eugenol inhibitory activity in lipoxygenase and cyclooxygenase pathways

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Francisco das Chagas Pereira de Andrade ◽  
Anderson Nogueira Mendes
Keyword(s):  
Side Effects ◽  
Inhibitory Activity ◽  
Inflammatory Process ◽  
Computational Analysis ◽  
Bioinformatics Analysis ◽  
Inflammatory Processes ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Gastric Irritation

Abstract Chronic inflammation is triggered by numerous diseases such as osteoarthritis, Crohn's disease and cancer. The control of the pro-inflammatory process can prevent, mitigate and/or inhibit the evolution of these diseases. Therefore, anti-inflammatory drugs have been studied as possible compounds to act in these diseases. This paper proposes a computational analysis of eugenol in relation to aspirin and diclofenac and analyzing the ADMET profile and interactions with COX-2 and 5-LOX enzymes, important enzymes in the signaling pathway of pro-inflammatory processes. Through the analysis of ADMET in silico, it was found that the pharmacokinetic results of eugenol are similar to NSAIDs, such as diclofenac and aspirin. Bioinformatics analysis using coupling tests showed that eugenol can bind to COX-2 and 5-LOX. These results corroborate with different findings in the literature that demonstrate anti-inflammatory activity with less gastric irritation, bleeding and ulcerogenic side effects of eugenol. The results of bioinformatics reinforce studies that try to propose eugenol as an anti-inflammatory compound that can act in the COX-2/5-LOX pathways, replacing some NSAIDs in different diseases.

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 Synthesis, anti-inflammatory, molecular docking and ADME studies of new derivatives of ketoprofen as cyclooxygenases inhibitor

2019 ◽  
pp. 125-139
Keyword(s):  
Molecular Docking ◽  
Side Effects ◽  
Nmr Spectra ◽  
Ft Ir ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Derivatives Of

The synthesis of new selective COX-2 enzyme is an approach for obtaining potent, anti-inflammatory drugs that have fewer side effects. Ketoprofen has a very low selectivity toward COX-2 enzyme and has a serious GIT side effects because it induces gastric ulcer. A new series of 4-thiazolidinones bearing ketoprofen moiety was designed, synthesized, and then evaluated as a new inhibitor of cyclooxygenase-2 (COX-2). Characterization and identification of the synthesized compounds were established by determination of 1H-NMR spectra,13C-NMR spectra, FT-IR spectroscopy, and physical properties. These newly synthesized compounds have been evaluated in vivo for their anti-inflammatory efficiency and in silico selectivity toward COX-2 throughout molecular docking by using GOLD.suite.v.5.6.2. All the tested. compounds via molecular. docking showed significant. activities when compared. With ketoprofen and diclofenac as references drugs, the results were consistent with the study of in in vivo acute. anti-inflammatory activity. Also, ADME studies had been accomplished in order to predict the absorption sites, bioavailability, topological polar surface Area (TPSA), and also drug-likeness. The ADME results reported that. All the synthesized. compounds can be absorbed by the GIT.

Synthesis, Design and Anti-inflammatory Activity of Novel 5-(Indol-3- yl)thiazolidinone Derivatives as COX-2 Inhibitors

2020 ◽  
Vol 17 ◽  
Author(s):  
Saad R. Atta-Allah ◽  
Ibrahim F. Nassar ◽  
Wael A. El-Sayed
Keyword(s):  
Inhibitory Activity ◽  
Mucosal Injury ◽  
Docking Study ◽  
Inflammatory Activity ◽  
Molecular Docking Study ◽  
Cox Inhibitors ◽  
High Preference ◽  
Ic50 Values ◽  
Cox 2 ◽  
Anti Inflammatory

Background & Objectives: New N-substituted 5-(oxoindolinyl)-2-thioxo- thiazolidinone derivatives were synthesized. Methods: The C2 -substituted thiazolidinone derivatives with piperidinyl and morpholinyl moieties in addition to the tetracyclic [(oxindolo)pyrazino]thiazolidine, the chloro- and amino- derivatives of the (indolyl)thiazolidinone ring system were also prepared. Results: The COX-2 inhibition activity of the synthesized compounds was investigated by studying their ability to inhibit the conversion of arachidonic acid to prostaglandin H2 (PGH2). Five of the tested candidates, substituted (oxonidolyl)thiazolidine derivatives (3a, 6f, 8b, 10 and 12) showed significant COX-2 inhibitory activity exhibiting IC50 values better than or close to the reference celecoxib. The anti-inflammatory activity was studied revealing that a number of compounds have shown good activities and compound 10 produced no significant mucosal injury. Conclusion: Molecular docking study was implemented to interpret the variable inhibitory activity of the newly synthesized compounds against COX enzyme.The results suggested that some of these derivatives could be active COX inhibitors possessing a high preference for COX-2.

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