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 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.

scholarly journals Anti-Arthritic and Anti-Inflammatory Potential of Spondias mangifera Extract Fractions: An In Silico, In Vitro and In Vivo Approach

Plants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 825
Author(s):  
Mohammad Khalid ◽  
Mohammed H. Alqarni ◽  
Ambreen Shoaib ◽  
Muhammad Arif ◽  
Ahmed I. Foudah ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Arthritis Score ◽  
Beneficial Effects ◽  
Tnf Α ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

The fruits of Spondias mangifera (S. mangifera) have traditionally been used for the management of rheumatism in the northeast region of India. The present study explores the probable anti-arthritis and anti-inflammatory potential of S. mangifera fruit extract’s ethanolic fraction (EtoH-F). To support this study, we first approached the parameters in silico by means of the active constituents of the plant (beta amyrin, beta sitosterol, oleonolic acid and co-crystallised ligands, i.e., SPD-304) via molecular docking on COX-1, COX-2 and TNF-α. Thereafter, the absorption, distribution, metabolism, excretion and toxicity properties were also determined, and finally experimental activity was performed in vitro and in vivo. The in vitro activities of the plant extract fractions were evaluated by means of parameters like 1,1-Diphenyl-2- picrylhydrazyl (DPPH), free radical-reducing potential, albumin denaturation, and protease inhibitory activity. The in vivo activity was evaluated using parameters like COX, TNF-α and IL-6 inhibition assay and arthritis score in Freund Adjuvant (CFA) models at a dose of 400 mg/kg b.w. per day of different fractions (hexane, chloroform, alcoholic). The molecular docking assay was performed on COX-1, COX-2 and TNF-α. The results of in vitro studies showed concentration-dependent reduction in albumin denaturation, protease inhibitors and scavenging activity at 500 µg/mL. Administration of the S. mangifera alcoholic fraction at the abovementioned dose resulted in a significant reduction (p < 0.01) in arthritis score, paw diameters, TNF-α, IL-6 as compared to diseased animals. The docking results showed that residues show a critical binding affinity with TNF-α and act as the TNF-α antagonist. The alcoholic fraction of S. mangifera extract possesses beneficial effects on rheumatoid arthritis as well as anti-inflammatory potential, and can further can be used as a possible agent for novel target-based therapies for the management of arthritis.

Synthesis, in vitro COX-1/COX-2 inhibition testing and molecular docking study of novel 1,4-benzoxazine derivatives

2019 ◽  
Vol 43 (26) ◽  
pp. 10305-10317 ◽  
Author(s):  
Mohammedumar M. Shaikh ◽  
Anuj P. Patel ◽  
Shivani P. Patel ◽  
Kishor H. Chikhalia
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Cox 2 ◽  
Cox 1

The present work deals with an efficient and straightforward synthesis, biological activity and molecular docking study of novel 1,4-benzoxazine 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 Synthesis, Cyclooxygenases Inhibition Activities and Interactions with BSA of N-substituted 1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diones Derivatives

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2934 ◽  
Author(s):  
Edward Krzyżak ◽  
Dominika Szkatuła ◽  
Benita Wiatrak ◽  
Tomasz Gębarowski ◽  
Aleksandra Marciniak
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Serum Albumins ◽  
Molecular Docking Study ◽  
Binding Interaction ◽  
Ic50 Value ◽  
Cox 2 ◽  
Therapeutic Activities ◽  
Cox 1

Inhibition of cyclooxygenase is the way of therapeutic activities for anti-inflammatory pharmaceuticals. Serum albumins are the major soluble protein able to bind and transport a variety of exogenous and endogenous ligands, including hydrophobic pharmaceuticals. In this study, a novel N-substituted 1H-pyrrolo[3–c]pyridine-1,3(2H)-diones derivatives were synthesized and biologically evaluated for their inhibitory activity against cyclooxygenases and interactions with BSA. In vitro, COX-1 and COX-2 inhibition assays were performed. Interaction with BSA was studied by fluorescence spectroscopy and circular dichroism measurement. The molecular docking study was conducted to understand the binding interaction of compounds in the active site of cyclooxygenases and BSA. The result of the COX-1 and COX-2 inhibitory studies revealed that all the compounds potentially inhibited COX-1 and COX-2. The IC50 value was found similar to meloxicam. The intrinsic fluorescence of BSA was quenched by tested compounds due to the formation of A/E–BSA complex. The results of the experiment and molecular docking confirmed the main interaction forces between studied compounds and BSA were hydrogen bonding and van der Waals force.

scholarly journals A New N-Substituted 1H-Isoindole-1,3(2H)-Dione Derivative—Synthesis, Structure and Affinity for Cyclooxygenase Based on In Vitro Studies and Molecular Docking

2021 ◽  
Vol 22 (14) ◽  
pp. 7678
Author(s):  
Dominika Szkatuła ◽  
Edward Krzyżak ◽  
Paulina Stanowska ◽  
Magdalena Duda ◽  
Benita Wiatrak
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Biological Properties ◽  
Molecular Ions ◽  
Molecular Docking Study ◽  
Lipinski’S Rule ◽  
Cox 2 ◽  
Probable Path ◽  
Cox 1

Isoindoline-1,3-dione derivatives constitute an important group of medicinal substances. In this study, nine new 1H-isoindole-1,3(2H)-dione derivatives and five potential pharmacophores were obtained in good yield (47.24–92.91%). The structure of the new imides was confirmed by the methods of elemental and spectral analysis: FT–IR, H NMR, and MS. Based on the obtained results of ESI–MS the probable path of the molecules decay and the hypothetical structure of the resulting pseudo-molecular ions have been proposed. The physicochemical properties of the new phthalimides were determined on the basis of Lipiński’s rule. The biological properties were determined in terms of their cyclooxygenase (COX) inhibitory activity. Three compounds showed greater inhibition of COX-2, three compounds inhibited COX-1 more strongly than the reference compound meloxicam. From the obtained results, the affinity ratio COX-2/COX-1 was calculated. Two compounds had a value greater than that of meloxicam. All tested compounds showed oxidative or nitrosan stress (ROS and RNS) scavenging activity. The degree of chromatin relaxation outside the cell nucleus was lower than the control after incubation with all test compounds. The newly synthesized phthalimide derivatives showed no cytotoxic activity in the concentration range studied (10–90 µM). A molecular docking study was used to determined interactions inside the active site of cyclooxygenases.

scholarly journals Synthesis, in vitro and in vivo biological evaluation, COX-1/2 inhibition and molecular docking study of indole-N-acylhydrazone derivatives

2018 ◽  
Vol 26 (20) ◽  
pp. 5388-5396 ◽  
Author(s):  
Ana Daura Travassos de Oliveira Moraes ◽  
Mirelly Dianne Santos de Miranda ◽  
Íris Trindade Tenório Jacob ◽  
Cézar Augusto da Cruz Amorim ◽  
Ricardo Olímpio de Moura ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Biological Evaluation ◽  
Molecular Docking Study ◽  
Cox 1

scholarly journals Biological Evaluation and Molecular Docking Studies of Dimethylpyridine Derivatives

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1093 ◽  
Author(s):  
Piotr Świątek ◽  
Katarzyna Gębczak ◽  
Tomasz Gębarowski ◽  
Rafal Urniaz
Keyword(s):  
Molecular Docking ◽  
Biological Evaluation ◽  
In Vivo Studies ◽  
Cyclooxygenase Inhibitors ◽  
Anticancer Activities ◽  
Molecular Docking Study ◽  
Binding Interaction ◽  
Cox 2 ◽  
Cox 1

Cyclooxygenase inhibitors as anti-inflammatory agents can be used in chemoprevention. Many in vitro and in vivo studies on human and animal models have explained the mechanisms of the chemopreventive effect of COX inhibitors such as: induction of apoptosis, inhibition of neoplasia, angiogenesis suppression, induction of cell cycle inhibition and inhibition of the expression of peroxisome proliferator-activated receptors. Here, biological evaluation of twelve different Schiff base derivatives of N-(2-hydrazine-2-oxoethyl)-4,6-dimethyl-2-sulfanylpyridine- 3-carboxamide are presented. Their in vitro anti-COX-1/COX-2, antioxidant and anticancer activities were studied. The molecular docking study was performed in order to understand the binding interaction of compounds in the active site of cyclooxygenases. Compounds PS18 and PS33 showed a significant inhibitory activity on COX-1 at lower concentrations compared to meloxicam and piroxicam. The IC50 of COX-1 of these compounds was 57.3 µM for PS18 and 51.8 µM for PS33. Out of the tested compounds, the highest therapeutic index was demonstrated by PS18, PS19, PS33, PS40 and PS41. Lower molar concentrations of these compounds inhibit the growth of cancer cells while not inhibiting the healthy cells. Compounds PS18, PS19 and PS33 simultaneously demonstrated a statistically-significant inhibition of COX-1 or COX-2. This opens up the possibility of applying these compounds in the chemoprevention of cancer.

scholarly journals Combined Use of Amentoflavone and Ledipasvir Could Interfere with Binding of Spike Glycoprotein of SARS-CoV-2 to ACE2: The Results of Molecular Docking Study

2020 ◽  
Author(s):  
Kateryna Miroshnychenko ◽  
Anna V. Shestopalova
Keyword(s):  
Molecular Docking ◽  
Binding Sites ◽  
Docking Study ◽  
Spike Glycoprotein ◽  
Molecular Docking Study ◽  
Docking Method ◽  
Combined Use ◽  
Virus Research

<p>In this study we used molecular docking method to test 248 drugs related to the virus research against spike glycoprotein of SARS-CoV-2. For ten top-ranked drugs the binding sites and interactions with spike glycoprotein were analyzed in detail. The best-scored ligand is the natural biflavonoid amentoflavone. Nine of twelve top-ranked ligands are drugs used for hepatitis C treatment. Among them are ledipasvir, paritaprevir, elbasvir, simeprevir, velpatasvir, glecaprevir and pibrentasvir. The two first-ranked ligands (amentoflavone and ledipasvir) have different binding sites, so their combined use may be effective, but the careful testing is required. We encourage other researchers to explore the combination of amentoflavone and ledipasvir against SARS-CoV-2 in vitro and in vivo.<br></p><p></p><p></p><p></p><p></p><p></p><p></p>

Sign in / Sign up

Export Citation Format

Share Document