Molecular docking study and molecular dynamic simulation of human cyclooxygenase-2 (COX-2) with selected eutypoids

Taidi, Loubna; Maurady, Amal; Britel, Mohammed Réda

doi:10.1080/07391102.2020.1823884

Cited by 20 publications

(27 citation statements)

References 31 publications

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“…Gibbs free energy of compound M. calabura with COX-2 The binding energy values obtained are almost similar to previous studies, which reported that the result of docking COX-2 with eutypoid A compound using Autodock Vina has a binding energy of -9.0 kcal/mol[30]. It indicates that the ligand binds strongly and is very stable to the COX-2 receptor.…”

supporting

confidence: 86%

Potential Adenostemma lavenia and Muntingia calabura Extracts to Inhibit Cyclooxygenase-2 Activity as a Therapeutic Strategy for Anti-inflammation: Experimental and Theoretical Studies

2022

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Continuous inflammation can cause new and more severe diseases, thus effective treatments are needed. One of the common inflammation treatments is given by reducing prostaglandins' production through the inhibition of COX-2 activity. This experiment aims to examine the potential application of plant extracts of Adenostemma lavenia and Muntingia calabura (Jamaica cherry) as anti-inflammatory agents in inhibiting COX-2 activity through in silico and in vitro assays. Molecular docking and molecular dynamics simulation were accomplished to evaluate the stability of the complex between COX-2 and ligands. The COX-2 inhibition was determined using the COX-2 Inhibitor Screening Assay KIT. Based on the docking results, the active compound from A. lavenia, ligand 1a,9b-dihydro-1H-cyclopropa[a]anthracene, has the lowest binding energy of -8.7 kcal/mol. In comparison, M. calabura contains 7-hydroxyflavone ligand with a Gibbs free energy of -9.1 kcal/mol. The molecular dynamics study demonstrates that COX-2 maintains its stability when forming interactions with selected compounds from all the tested extracts. The results of the COX-2 inhibition test showed that 96% EtOH extract of A. Lavenia at concentrations of 25 and 100 ppm had an inhibitory activity of 98%; meanwhile, 70% and 96% EtOH extracts of M. calabura at 1000 ppm concentration could inhibit COX-2 activity up to 100%. The results demonstrate that both plants show potential anti-inflammatory activity.

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supporting

confidence: 86%

Potential Adenostemma lavenia and Muntingia calabura Extracts to Inhibit Cyclooxygenase-2 Activity as a Therapeutic Strategy for Anti-inflammation: Experimental and Theoretical Studies

2022

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“…Physicochemical parameters such as molecular mass, log P water (miLogP), the number of OH − , and H + were analyzed via swissADME software ( http://www.swissadme.ch/ ) to evaluate the remedy ability of the best-docked ligand models. 31 , 32 The pharmaceutical drug properties of the synthetic compound FA2 were evaluated according to the Lipinski’s rule of five (RO5). 33 …”

Section: Methodsmentioning

confidence: 99%

“…The ADMET properties of the FA2 compound were predicted via computational tools, eg, SwissADME ( http://www.swissadme.ch/ ) 34 and PreADMET ( https://preadmet.bmdrc.kr/ ). 31 Cardiotoxicity was also predicted via predherg software ( http://predherg.labmol.com.br ).…”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis and Pharmacological Evaluation of 2-(3-BenzoyI-4-Hydroxy-1,1-Dioxido-2H-Benzo[e][1,2]thiazin-2-yI)-N-(2-Bromophenyl) Acetamide as Antidiabetic Agent

Rashid¹,

Ahmad²,

Ashfaq³

et al. 2022

DDDT

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Purpose The present study is based on screening new and potent synthetic heterocyclic compounds as anti-diabetic drugs using various computational tools, lab experiments, and animal models. Methods A potent synthetic compound 2-(3-benzoyl-4-hydroxy-1,1-dioxido-2 H -benzo[ e ][1,2]thiazin-2-yl)-1-(2-bromophenyl) acetamide (FA2) was checked against diabetes and screened via enzyme inhibition assays, enzyme kinetics against alpha-glucosidase and alpha-amylase. Protein–ligand interaction was analyzed via molecular docking and toxicological analysis via ADMET. Experimental animals were used to examine the compound FA2 safety, delivery, and check various biochemical tests related to diabetes like fasting glucose sugar, cholesterol, triglyceride, HbAc1, creatinine, and insulin level. Histography of liver, kidney, and pancreas was also performed. Results Results showed that FA2 had binding energy of ‐7.02 Kcal/mol and ‐6.6 kcal/mol against α‐glucosidase (PDB ID: 2ZE0) and α‐amylase (PDB ID: 1B2Y), respectively. Moreover, in vitro enzyme inhibition assays and enzyme kinetics against α‐glucosidase and α‐amylase were performed, and FA2 showed IC50 at 5.17 ± 0.28 µM and 18.82 ± 0.89 µM concentrations against α‐glucosidase and α‐amylase, respectively. Kinetics studies showed that the FA2 compound impeded α‐glucosidase and α-amylase as a non-competitive mode of inhibition with Ki’ values −0.320 ± 0.001 and 0.141 ± 0.01, respectively. FA2 was further analyzed on alloxan-induced mice for 21 days. Biochemical tests (fasting glucose sugar, cholesterol, triglyceride, HbAc1, creatinine, and insulin levels) and histological examination of liver and kidney showed that the FA2 compound showed better results than acarbose. Histology of pancreas found to show the maintenance of normal pancreatic acini and Langerhans islets in FA2 treated mice compared to acarbose and nontreated diabetic controls. Conclusion Investigating anti-diabetic potential of FA2 compound showed that the selected benzothiazine derivative has tremendous importance in reducing dose concentration and side effects.

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“…To elucidate the detailed interaction between HY and NF-κB pathway, we performed molecular docking using Autodock 1.5.6 software and Gold 5.2 software according to previously published methods [38,39]. In brief, ligand molecule HY was constructed by the ChemBio3D Ultra 14.0 software using mm2 to optimize the structure to energy minimization to create a sdf file for later use.…”

Section: Molecular Modelingmentioning

confidence: 99%

Discovery of Phenolic Glycoside from Hyssopus cuspidatus Attenuates LPS-Induced Inflammatory Responses by Inhibition of iNOS and COX-2 Expression through Suppression of NF-κB Activation

Liu

Wang

et al. 2021

IJMS

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It seems quite necessary to obtain effective substances from natural products against inflammatory response (IR) as there are presently clinical problems regarding accompanying side effects and lowered quality of life. This work aimed to investigate the abilities of hyssopuside (HY), a novel phenolic glycoside isolated from Hyssopus cuspidatus (H. cuspidatus), against IR in lipopolysaccharide (LPS)-induced RAW 264.7 cells and mouse peritoneal macrophages. The results indicated that HY could reduce nitric oxide (NO) production and inhibit the production and secretion of pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in LPS-stimulated macrophages. Moreover, data from the immunofluorescence study showed that HY suppressed nuclear translocation of nuclear factor-kappa B (NF-κB) upon LPS induction. The Western blot results suggested that HY reversed the LPS-induced degradation of IκB (inhibitor of NF-κB), which is normally required for the activation of NF-κB. Meanwhile, the overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) diminished significantly with the presence of HY in response to LPS stimulation. On the other hand, HY had a negligible impact on the activation of mitogen-activated protein kinase (MAPK) pathways. Moreover, an in silico study of HY against four essential proteins/enzymes revealed that COX-2 was the most efficient enzyme for the interaction, and binding of residues Phe179, Asn351, and Ser424 with HY played crucial roles in the observed activity. The structure analysis indicated the typical characterizations with phenylethanoid glycoside contributed to the anti-inflammatory effects of HY. These results indicated that HY manipulated its anti-inflammatory effects mainly through blocking the NF-κB signal transduction pathways. Collectively, we believe that HY could be a potential alternative phenolic agent for alleviating excessive inflammation in many inflammation-associated diseases.

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Molecular docking study and molecular dynamic simulation of human cyclooxygenase-2 (COX-2) with selected eutypoids

Cited by 20 publications

References 31 publications

Potential <i>Adenostemma lavenia</i> and <i>Muntingia calabura</i> Extracts to Inhibit Cyclooxygenase-2 Activity as a Therapeutic Strategy for Anti-inflammation: Experimental and Theoretical Studies

Potential <i>Adenostemma lavenia</i> and <i>Muntingia calabura</i> Extracts to Inhibit Cyclooxygenase-2 Activity as a Therapeutic Strategy for Anti-inflammation: Experimental and Theoretical Studies

Design, Synthesis and Pharmacological Evaluation of 2-(3-BenzoyI-4-Hydroxy-1,1-Dioxido-2H-Benzo[e][1,2]thiazin-2-yI)-N-(2-Bromophenyl) Acetamide as Antidiabetic Agent

Discovery of Phenolic Glycoside from Hyssopus cuspidatus Attenuates LPS-Induced Inflammatory Responses by Inhibition of iNOS and COX-2 Expression through Suppression of NF-κB Activation

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