Synthesis, Molecular Docking and In Vivo Biological Evaluation of Iminostilbene Linked 1,2,3-Triazole Pharmacophores as Promising AntiAnxiety and Anti-Inflammatory Agents

2021 ◽  
Vol 17 ◽  
Author(s):  
Kariyappa N. Ankali ◽  
Javarappa Rangaswamy ◽  
Mallappa Shalavadi ◽  
Nagaraja Naik
Keyword(s):  
Molecular Docking ◽  
Cycloaddition Reaction ◽  
Triazole Ring ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Gaba A ◽  
Chemical Structures ◽  
Rat Paw Edema ◽  
Anti Inflammatory

Background: Iminostilbene and 1,2,3-triazole ring containing compounds are considered as beneficial substrates in drug design. Objectives: This study was aimed at the synthesis of novel series of iminostilbene linked 1,2,3- triazole pharmacophores (7c-n) by Cu(I) catalyzed 1,3 dipolar cycloaddition reaction between 5- (Prop-2-yn-1-yl)-5H-dibenzo[b,f]azepine (7b) and various substituted azidobenzene derivatives (3cn). Methods: The chemical structures of compounds were confirmed by 1 H NMR, 13C NMR, LC-MS and molecular docking studies were carried out through HEX docking software. Results: The in vivo anti anxiety capacity of the compounds was evaluated by using “elevated plus maze” (EPM), anxiety model. The results exhibited that compounds (7d, 7e, 7j and 7k) have a higher anti anxiety effect close to diazepam. The anti-inflammatory activities of the synthesized compounds were evaluated by “Carrageenan-induced rat paw edema” model, compounds (7b, 7c, 7d, 7f, and 7j) demonstrated statistically significant inflammatory activity. Molecular docking analysis revealed that compounds (7d, 7e and 7j) bound to GABA(A) proteins show more efficiency when compared to the other analogues in the series. Conclusion: These results suggest that compounds (7b, 7c, 7d, 7e, 7f, and 7j) can be considered as novel candidates for anti-anxiety and anti-inflammatory agents. Moreover, docking method was used to elucidate anti-anxiety effect of compounds. This study furnished insight into the molecular interactions of synthesized compounds with their physiological targets, and the potential to develop bioactive heterocyclic compounds.

scholarly journals Heterocycles 48. Synthesis, Characterization and Biological Evaluation of Imidazo[2,1-b][1,3,4]Thiadiazole Derivatives as Anti-Inflammatory Agents

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2425 ◽  
Author(s):  
Anamaria Cristina ◽  
Denisa Leonte ◽  
Laurian Vlase ◽  
László Bencze ◽  
Silvia Imre ◽  
...  
Keyword(s):  
Side Effects ◽  
Inflammatory Diseases ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Standard Drug ◽  
Rat Paw Edema ◽  
Thiadiazole Derivatives ◽  
Cox 2 ◽  
Anti Inflammatory

Non-steroidal anti-inflammatory drugs (NSAIDs) are an important pharmacological class of drugs used for the treatment of inflammatory diseases. They are also characterized by severe side effects, such as gastrointestinal damage, increased cardiovascular risk and renal function abnormalities. In order to synthesize new anti-inflammatory and analgesic compounds with a safer profile of side effects, a series of 2,6-diaryl-imidazo[2,1-b][1,3,4]thiadiazole derivatives 5a–l were synthesized and evaluated in vivo for their anti-inflammatory and analgesic activities in carrageenan-induced rat paw edema. Among all compounds, 5c showed better anti-inflammatory activity compared to diclofenac, the standard drug, and compounds 5g, 5i, 5j presented a comparable antinociceptive activity to diclofenac. None of the compounds showed ulcerogenic activity. Molecular docking studies were carried out to investigate the theoretical bond interactions between the compounds and target, the cyclooxygenases (COX-1/COX-2). The compound 5c exhibited a higher inhibition of COX-2 compared to diclofenac.

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 Synthesis, Molecular Modelling and Biological Evaluation of Novel Pyrimidine Derivatives as Anti-inflammatory Agents

2020 ◽  
pp. 49-67
Author(s):  
Naglaa Mohamed Ahmed ◽  
Shahira Nofal ◽  
Samir Mohamed Awad
Keyword(s):  
Docking Studies ◽  
Biological Evaluation ◽  
Inflammatory Activity ◽  
Pyrimidine Derivatives ◽  
Reference Drug ◽  
Rat Paw Edema ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1 ◽  
Good Agreement

Aim: As part of ongoing studies in developing new anti-inflammatory agents, 2-thioxo-1,2,3,4-tetrahydropyrimidine derivative 1 was synthesized by direct Biginelli condensation and used for the synthesis of novel series of  pyrimidin-2-thione derivatives  (2a-d to 7a-b). Materials and Methods: All compounds were examined for their anti-inflammatory activity using the carrageenan-induced rat paw edema assay in comparison to ibuprofen, as a reference drug. Molecular docking studies were carried out using SYBLYL-X v.2.1 software. Study Design: A series of pyrimidine derivatives were synthesized by a simple and available method leads to a molecule of promising anti-inflammatory activity, the docking studies show good agreement with anti-inflammatory results. Future researches are recommended to assure the importance of these new derivatives for various applications. Place and Duration of Study: Pharmaceutical Organic Chemistry Department and Pharmacology and Toxicology Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt, between February 2018 and March 2019. Results: Compounds showed 61 to 86% anti-inflammatory activity where-as ibuprofen showed 69% activity. Compounds 2a, 2b, 2c, 2d, 3a, 3b, 3c, 3d, 7a, 7b induced strong anti-inflammatory activity, comparable with that of ibuprofen, they showed significantly difference at 4h post-carrageenan. Compound 3c (86%) showed the best result of edema inhibition in rats. Moreover, compounds 1, 2c and 3c were subjected to in vitro enzyme assay investigations against COX-1 and COX-2. All tested compounds showed higher potency towards COX-2 over COX-1. Compound 3c realized higher potency towards COX-2 (IC50= 0.046 μM) than compounds 1(IC50= 0.21 μM) and 2c (IC50=0.11 μM) as well as ibuprofen (IC50= 43.628 μM). Structure-activity relationship (SAR) has been discussed. Conclusion: A series of pyrimidine derivatives were synthesized by a simple and available method gave a molecule of promising anti-inflammatory activity, the docking studies showed good agreement with anti-inflammatory results.

Potential Bioactive glycosylated flavonoids as SARS-CoV-2 Main protease Inhibitors: A molecular Docking Study

2020 ◽  
Author(s):  
sabri ahmed cherrak ◽  
merzouk hafida ◽  
mokhtari soulimane nassima
Keyword(s):  
Molecular Docking ◽  
Data Bank ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Chemical Structures ◽  
In Vivo Experiments ◽  
Main Protease

A novel (COVID-19) responsible of acute respiratory infection closely related to SARS-CoV has recently emerged. So far there is no consensus for drug treatment to stop the spread of the virus. Discovery of a drug that would limit the virus expansion is one of the biggest challenges faced by the humanity in the last decades. In this perspective, testing existing drugs as inhibitors of the main COVID-19 protease is a good approach.Among natural phenolic compounds found in plants, fruit, and vegetables; flavonoids are the most abundant. Flavonoids, especially in their glycosylated forms, display a number of physiological activities, which makes them interesting to investigate as antiviral molecules.The flavonoids chemical structures were downloaded from PubChem and protease structure 6lu7 was from the Protein Data Bank site. Molecular docking study was performed using AutoDock Vina. Among the tested molecules Quercetin-3-O-rhamnoside showed the highest binding affinity (-9,7 kcal/mol). Docking studies showed that glycosylated flavonoids are good inhibitors for the covid-19 protease and could be further investigated by in vitro and in vivo experiments for further validation.

Synthesis, In-vitro and In-silico Anti-inflammatory activity of new Thiazole derivatives

2021 ◽  
pp. 4253-4260
Author(s):  
Kumaraswamy Gullapelli ◽  
Ravichandar Maroju ◽  
Ramchander Merugu
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Inflammatory Activity ◽  
Moderate Activity ◽  
Spectroscopic Techniques ◽  
Thiazole Derivatives ◽  
Chemical Structures ◽  
Anti Inflammatory ◽  
High Inhibition

The present study is aiming at synthesis of new heterocycles like benzimidazole nucleus containing Pyrazole, isoxazole and thiazoles. The title compounds were synthesized from 4-(1H-benzo[d]imidazol-2-yl) oxazol-2-amine (1). The title compounds were evaluated for their in vitro anti-inflammatory activity and showed excellent to moderate activity and molecular docking studies were supporting anti-inflammatory activity exhibiting high inhibition constant and binding energy. The chemical structures of the synthesised compounds were characterized by IR, 1HNMR, Mass spectroscopic techniques.

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