scholarly journals In vitro and molecular docking studies of an antiinflammatory scaffold with human peroxiredoxin 5 and tyrosine kinase receptor

2020 ◽  
Vol 16 (11) ◽  
pp. 929-936
Author(s):  
R Bharathi ◽  
◽  
Keyword(s):  
Molecular Docking ◽  
Tyrosine Kinase ◽  
Diclofenac Sodium ◽  
Docking Studies ◽  
Tyrosine Kinase Receptor ◽  
Docking Analysis ◽  
Elemental Analyses ◽  
Anti Inflammatory ◽  
Potential Inhibitors

A new series of 4-(3-(2-amino-3,5-dibromophenyl)-1-(4-substitutedbenzoyl)-4,5-dihydro-1H-pyrazol-5-yl)benzonitrile (4a-h) compounds were synthesized and evaluated for in-vitro anti-inflammatory activities. The spectral (IR, NMR) and elemental analyses data of the product indicated the formation of new pyrazoles 4a-h. Compound 4e exhibited potent anti-inflammatory property with 85.45 % inhibitions. This value was compared with standard diclofenac sodium. This data is explained using molecular docking analysis of receptor-ligand binding. These results demonstrated that pyrazole derivatives are potential inhibitors of Human Peroxiredoxin 5 and Tyrosine kinase receptor in the treatment of inflammation related illness.

scholarly journals Design, Synthesis and Comprehensive Investigations of Pyrrolo[3,4-d]pyridazinone-Based 1,3,4-Oxadiazole as New Class of Selective COX-2 Inhibitors

2020 ◽  
Vol 21 (24) ◽  
pp. 9623
Author(s):  
Łukasz Szczukowski ◽  
Edward Krzyżak ◽  
Adrianna Zborowska ◽  
Patrycja Zając ◽  
Katarzyna Potyrak ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
One Pot ◽  
Design Synthesis ◽  
Biological Studies ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Dna Strand ◽  
Cox 2 Inhibitors

The long-term use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in treatment of different chronic inflammatory disorders is strongly restricted by their serious gastrointestinal adverse effects. Therefore, there is still an urgent need to search for new, safe, and efficient anti-inflammatory agents. Previously, we have reported the Mannich base-type derivatives of pyrrolo[3,4-d]pyridazinone which strongly inhibit cyclooxygenase, have better affinity to COX-2 isoenzyme and exert promising anti-oxidant activity. These findings encouraged us to perform further optimization of that structure. Herein, we present the design, synthesis, molecular docking, spectroscopic, and biological studies of novel pyrrolo[3,4-d]pyridazinone derivatives bearing 4-aryl-1-(1-oxoethyl)piperazine pharmacophore 5a,b–6a,b. The new compounds were obtained via convenient, efficient, one-pot synthesis. According to in vitro evaluations, novel molecules exert no cytotoxicity and act as selective COX-2 inhibitors. These findings stay in good correlation with molecular modeling results, which additionally showed that investigated compounds take a position in the active site of COX-2 very similar to Meloxicam. Moreover, all derivatives reduce the increased level of reactive oxygen and nitrogen species and prevent DNA strand breaks caused by oxidative stress. Finally, performed spectroscopic and molecular docking studies demonstrated that new compound interactions with bovine serum albumin (BSA) are moderate, formation of complexes is in one-to-one ratio, and binding site II (subdomain IIIA) is favorable.

scholarly journals Synthesis, Anti-Inflammatory Activity and Molecular Docking Studies of 1,4,5,6-Tetrahydropyrimidine-2-Carboxamides

2020 ◽  
Vol 27 (3) ◽  
pp. 353-365
Author(s):  
Volodymyr Ya. Horishny ◽  
Pavlo V. Zadorozhnii ◽  
Ivanna V. Horishnia ◽  
Vasyl S. Matiychuk
Keyword(s):  
Molecular Docking ◽  
Side Effects ◽  
Docking Studies ◽  
Inflammatory Activity ◽  
Cox Inhibitors ◽  
White Rats ◽  
Urgent Task ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs in the world. The widespread use of NSAIDs is associated with a number of serious side effects and complications observed for both selective and non-selective COX inhibitors. Therefore, the search for new COX inhibitors, which along with their effectiveness will have minimal side effects, is a very important and urgent task. Methods: This work studied the synthesis of new 1,4,5,6-tetrahydropyrimidine-2-carboxamides based on the reaction of 2-morpholin-4-yl-N-(het)aryl-2-thioxoacetamides with 1,3-diaminopropane. All obtained compounds were tested for anti-inflammatory activity in vitro and in silico conditions. All synthesized 1,4,5,6-tetrahydropyrimidine-2-carboxamides were tested for influence on the course of the exudative phase of the inflammatory process based on the carrageenan model of paw edema of laboratory nonlinear heterosexual white rats weighing 220-250 g, using Diclofenac as a reference. Optimization of the geometry of the studied structures and molecular docking was carried out using the ArgusLab 4.0.1 software package. Results: The target products were obtained with yields of 71-98% and easily isolated from the reaction mixture. The best anti-inflammatory activity was found in N-(4-chlorophenyl)-1,4,5,6-tetrahydropyrimidine-2-carboxamide and in N-[4-chloro-3-(trifluoromethyl)phenyl]-1,4,5,6-tetrahydropyrimidine-2-carboxamide, suppression of the inflammatory response was 46.7 and 46.4%, respectively. The results of molecular docking with COX-1 and COX-2 enzymes were in good agreement with the experimental data, R2 ˃ 0.92 and R2 ˃ 0.83, respectively. Conclusion: The compounds under study were shown to be promising as potential anti-inflammatory agents.

scholarly journals Novel inhibitors designing against the potential drug target of Plasmodium falciparum M17 Leucyl Aminopeptidase - PfM17LAP

2021 ◽  
Author(s):  
Govinda Rao Dabburu ◽  
Manish Kumar ◽  
Naidu Subbarao
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Docking ◽  
Drug Target ◽  
Docking Studies ◽  
Simulation Studies ◽  
Docking Analysis ◽  
Discovery Studio ◽  
Potential Inhibitors ◽  
Key Words Malaria ◽  
Leucyl Aminopeptidase

Abstract: Malaria is one of the major disease of concern worldwide especially in the African regions. According to the recent WHO reports, African regions share 95% of the total deaths worldwide that occurs due to malaria. Plasmodium falciparum M17 Leucyl Aminopeptidase (PfM17LAP) plays an important role in the regulation of amino acids release and for the survival of the parasite. We performed molecular docking and simulation studies to find the potential inhibitors against PfM17LAP using ChEMBL antimalarial library. Molecular docking studies and post-docking analysis revealed that molecules CHEMBL369831 and CHEMBL176888 showed better binding than the reference molecule BESTATIN. LibDock and X-SCORES of molecules BES, CHEMBL369831 and CHEMBL176888 are 130.071, 230.38, 223.56 and -8.75 Kcal/mol, -10.90 Kcal/mol, -11.05 Kcal/mol respectively. ADMET profiling of the top ten ranked molecules was done by using the Discovery Studio. Molecular dynamic studies revealed that the complex PfM17LAP-CHEMBL369831 is stable throughout the simulation. Finally, we have reported novel inhibitors which possess more binding affinity towards PfM17LAP. Key words: Malaria, M17 Leucyl Aminopeptidase, ADMET, X-SCORE

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.

2-Aryl-3-(2-morpholinoethyl)thiazolidin-4-ones: Synthesis, anti-inflammatory in vivo, cytotoxicity in vitro and molecular docking studies

2016 ◽  
Vol 118 ◽  
pp. 259-265 ◽  
Author(s):  
Daniela Pires Gouvea ◽  
Flávia Aleixo Vasconcellos ◽  
Gabriele dos Anjos Berwaldt ◽  
Amilton Clair Pinto Seixas Neto ◽  
Gerferson Fischer ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Anti Inflammatory ◽  
In Vivo Cytotoxicity

scholarly journals Biological Evaluation and Molecular Docking Studies of Benzalkonium Ibuprofenate

2020 ◽  
Author(s):  
Kodakkat Parambil Safna Hussan ◽  
Mohamed Shahin Thayyil ◽  
Thaikadan Shameera Ahamed ◽  
Karuvanthodi Muraleedharan
Keyword(s):  
Biological Activity ◽  
Molecular Docking ◽  
Performance Enhancement ◽  
Docking Study ◽  
Docking Studies ◽  
Inflammatory Activity ◽  
Molecular Docking Study ◽  
Anti Inflammatory ◽  
Delivery Options

The third-generation ionic liquids (ILs), which are being used to produce double active pharmaceutical ingredients (d-APIs) with tunable biological activity along with novel performance, enhancement, and delivery options, have been revolutionizing the area of drug discovery since the past few decades. Herein we report the in vitro antibacterial and anti-inflammatory activity of benzalkonium ibuprofenate (BaIb) that are being used as in-house d-API, with a particular focus on its interaction with respective protein target through molecular docking study. The evaluation of the biological activity of BaIb with the antibacterial and anti-inflammatory target at the molecular level revealed that the synthesized BaIb could be designed as a potential double active drug since it retains the antibacterial and anti-inflammatory activity of its parent drugs, benzalkonium chloride (BaCl) and sodium ibuprofenate (NaIb), respectively.

scholarly journals Synthesis, Molecular Docking Analysis and in Vitro Biological Evaluation of Some New Heterocyclic Scaffolds-Based Indole Moiety as Possible Antimicrobial Agents

2022 ◽  
Vol 8 ◽  
Author(s):  
Entesar A. Hassan ◽  
Ihsan A. Shehadi ◽  
Awatef M. Elmaghraby ◽  
Hadir M. Mostafa ◽  
Salem E. Zayed ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antimicrobial Agents ◽  
Antibacterial Activities ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Standard Drug ◽  
Docking Analysis ◽  
Excellent Activity ◽  
New Compounds

In the present study, a general approach for the synthesis of 1-(1H-indol-3-yl)-3,3-dimercaptoprop-2-en-1-one (1) and 5-(1H-indol-3-yl)-3H-1,2-dithiole-3-thione (2) was performed. They are currently used as efficient precursors for the synthesis of some new compounds bearing five- and/or six-membered heterocyclic moieties, e.g., chromenol (3, 4), 3,4-dihydroquinoline (7, 8) and thiopyran (10, 12)-based indole core. In addition, molecular docking studies were achieved, which showed that all the newly synthesized compounds are interacting with the active site region of the target enzymes, the targets UDP-N-acetylmuramatel-alanine ligase (MurC), and human lanosterol14α-demethylase, through hydrogen bonds and pi-stacked interactions. Among these docked ligand molecules, the compound (9) was found to have the minimum binding energy (−11.5 and −8.5 Kcal/mol) as compared to the standard drug ampicillin (−8.0 and −8.1 Kcal/mol) against the target enzymes UDP-N-acetylmuramatel-alanine ligase (MurC), and Human lanosterol14α-demethylase, respectively. Subsequently, all new synthesized analogues were screened for their antibacterial activities against Gram-positive (Bacillus subtilis), and Gram-negative bacteria (Escherichia coli), as well as for antifungal activities against Candida albicans and Aspergillus flavus. The obtained data suggest that the compounds exhibited good to excellent activity against bacterial and fungi strains. The compound (E)-2-(6-(1H-indole-3-carbonyl)-5-thioxotetrahydrothieno [3,2-b]furan-2(3H)-ylidene)-3-(1H-indol-3-yl)-3-oxopropanedithioic acid (9) showed a high binding affinity as well as an excellent biological activity. Therefore, it could serve as the lead for further optimization and to arrive at potential antimicrobial agent.

Design, Synthesis, Antioxidant, Anti-inflammatory Activity and Molecular Docking Studies of Novel 3,4,5-Trisubstituted-1,2,4-Triazole Derivatives Bearing Benzimidazole Moiety

2020 ◽  
Vol 17 ◽  
Author(s):  
Ramamurthy Katikireddy ◽  
Ramu Kakkerla ◽  
M.P.S. Murali Krishna ◽  
Gandamalla Durgaiah ◽  
Narasimha Reddy Yellu
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Biological Data ◽  
Inflammatory Activity ◽  
Design Synthesis ◽  
Molecular Docking Studies ◽  
Cox 2 ◽  
Anti Inflammatory

: 5-(7-Methyl-2-propyl-1H-benzo[d]imidazol-5-yl)-4-phenyl-4H-1,2,4-triazole-3-thiols(6a-i) have been synthesized from key intermediate 7-methyl-2-propyl-1H-benzo[d]imidazole-5-carbohydrazide(3). The hydrazide was treated with different aryl isothiocyanatesto give corresponding thiosemicarbazone derivatives, which underwent cyclization in 4N sodium hydroxide to affordcorresponding title compound. All the compounds evaluated for their in vitro antioxidant and in vivo anti-inflammatory activity. From the results, compounds 6b and 6e have shown potential antioxidant and anti-inflammatory activity. The biological data was further supported by molecular docking studies, which revealed the binding pattern and the affinity of the molecules in the active site of COX-2.

Synthesis, Anti-inflammatory, Antimicrobial Potential and Molecular Docking Studies of 4,5-Disubstituted-1,2,4-Triazole Thioacetate Derivatives

2019 ◽  
Vol 16 (7) ◽  
pp. 734-745 ◽  
Author(s):  
Muhammad Nouman Arif ◽  
Humaira Nadeem ◽  
Rehan Zafar Paracha ◽  
Arif-ullah Khan ◽  
Muhammad Imran ◽  
...  
Keyword(s):  
Docking Studies ◽  
Inflammatory Activity ◽  
Biological Assessment ◽  
Maximum Effect ◽  
Docking Analysis ◽  
Paw Oedema ◽  
Anti Inflammatory ◽  
Rat Paw

Background: In the present study synthesis and biological assessment of nine new ethyl [(4,5-disubstituted- 4H-1,2,4-triazol-3-yl)sulfanyl]acetate derivatives 2(a-i) is performed. Methods: The title compounds were characterized by their analytical and spectral data. All the synthesized compounds were screened for their in vivo anti-inflammatory activity using carrageenaninduced rat paw oedema method and in vitro antimicrobial activity. All the compounds exhibited good anti-inflammatory activity; especially compound 2h produced the maximum effect i.e., 62.5 % comparable to that of standard, diclofenac. The antimicrobial screening results indicated that some of the newly synthesized compounds showed good antibacterial activity, especially against Escherichia coli. Results: All the synthesized thioacetate derivatives of triazoles were also studied for their interactions with the enzymes COX-I and COX-II, two important targets of inflammation pathway, through docking analysis. All the compounds showed good binding affinities with both the enzymes with a maximum value of -8.1 for 2e kcal/mol against COX-I. Conclusion: Docking analysis predicted that our compounds reduce inflammation nonselectively by inhibiting both COX-I and COX-II of inflammatory pathway just like other nonselactive NSAIDS.

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