Protease activated receptor-2 (PAR2): possible target of phytochemicals

Kakarala, Kavita Kumari; Jamil, Kaiser

doi:10.1080/07391102.2014.986197

Cited by 12 publications

(5 citation statements)

References 80 publications

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“…The ligand binding energy of each of the 20 phytocompounds required to inhibit AChE was estimated using the prime molecular mechanics‐generalized born surface area (MM-GBSA) module in the Schrodinger Suite 2014 [26], [27]. The total free energy binding (digibind, kcal/mol) was estimated as follows using the software:normalΔnormalGnormalbnormalinormalnnormald=Gnormalcnormalonormalmnormalpnormallnormalenormalx-true(Gprotein+Gligandtrue)Where each energy term is a combination of G=molecular mechanics energies (MME)+GSGB (SGB solvation model for polar solvation)+GNP (non-polar solvation) [28] coulomb energy, covalent binding energy, Vander Waals energy, lipophilic energy, GB electrostatic solvation energy, prime energy, hydrogen-bonding energy, hydrophobic contact, and self-contact correction [29]. We then used this score to rank the ligand-protein Glide XP docked complex.…”

Section: Tools and Methodsmentioning

confidence: 99%

Novel ligand-based docking; molecular dynamic simulations; and absorption, distribution, metabolism, and excretion approach to analyzing potential acetylcholinesterase inhibitors for Alzheimer's disease

Vijayakumar¹,

Palani²,

Prabhu³

et al. 2018

Journal of Pharmaceutical Analysis

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Acetylcholinesterase (AChE) plays an important role in Alzheimer's disease (AD). The excessive activity of AChE causes various neuronal problems, particularly dementia and neuronal cell deaths. Generally, anti-AChE drugs induce some serious neuronal side effects in humans. Therefore, this study sought to identify alternative drug molecules from natural products with fewer side effects than those of conventional drugs for treating AD. To achieve this, we developed computational methods for predicting drug and target binding affinities using the Schrodinger suite. The target and ligand molecules were retrieved from established databases. The target enzyme has 539 amino acid residues in its sequence alignment. Ligand molecules of 20 bioactive molecules were obtained from different kinds of plants, after which we performed critical analyses such as molecular docking; molecular dynamic (MD) simulations; and absorption, distribution, metabolism, and excretion (ADME) analysis. In the docking studies, the natural compound rutin showed a superior docking score of −12.335 with a good binding energy value of −73.313 kcal/mol. Based on these findings, rutin and the target complex was used to perform MD simulations to analyze rutin stability at 30 ns. In conclusion, our study demonstrates that rutin is a superior drug candidate for AD. Therefore, we propose that this molecule is worth further investigation using in vitro studies.

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Section: Tools and Methodsmentioning

confidence: 99%

Novel ligand-based docking; molecular dynamic simulations; and absorption, distribution, metabolism, and excretion approach to analyzing potential acetylcholinesterase inhibitors for Alzheimer's disease

Vijayakumar¹,

Palani²,

Prabhu³

et al. 2018

Journal of Pharmaceutical Analysis

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“…According to the results regarding the structure of molecular docking, acarbose and naringenin were buried in the α-glucosidase binding site. In the MD studies, root mean square deviation (RMSD) was used as an indicator that evaluates the average conformational change of an atom concerning reference conformations [ 42 ]. The RMSD of acarbose was initially at 0.9 Å, which then fluctuated up to 4 Å in 2.5 ns ( Figure 3 ).…”

Section: Resultsmentioning

confidence: 99%

Molecular Docking and Molecular Dynamics Studies of Antidiabetic Phenolic Compound Isolated from Leaf Extract of Englerophytum magalismontanum (Sond.) T.D.Penn.

et al. 2022

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Englerophytum magalismontanum, a medicinal plant with ethnopharmacology use, has a dearth of information regarding its antidiabetic properties. This study evaluated the crude methanol leaf extract of E. magalismontanum and its fractions for total phenolic content, antioxidant activity, and digestive enzymes (α-amylase and α-glucosidase) inhibitory activity using standard methods. The total phenolic content (56.53 ± 1.94 mg GAE/g dry extract) and DPPH Trolox antioxidant equivalent (TAE) (1.51 ± 0.66 µg/mL) of the methanol fraction were the highest among the fractions. The IC50 values of the methanol fraction against α-amylase (10.76 ± 1.33 µg/mL) and α-glucosidase (12.25 ± 1.05 µg/mL) activities were also high. Being the most active, the methanol fraction was subjected to bio-assay guided column chromatography-based enzyme inhibition to obtain a pure compound. The phenolic compound isolated and identified as naringenin inhibited α-amylase and α-glucosidase with IC50 of 5.81 ± 2.14 µg/mL and 4.77 ± 2.99 µg/mL, respectively. This is the first study to isolate naringenin from E. magalismontanum extract. The molecular docking and molecular dynamics studies demonstrated naringenin as a promising lead compound in comparison to acarbose for the treatment of diabetes through the inhibition of α-glucosidase activity.

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“…Where each energy term is a combination of G = Molecular mechanics energies (MME) + GSGB (SGB solvation model for polar solvation) + GNP (non-polar solvation) (Kakarala and Jamil, 2015) coulomb energy, covalent binding energy, Vander Waals energy, lipophilic energy, GB electrostatic solvation energy, prime energy, hydrogen-bonding energy, hydrophobic contact, and self-contact correction (Lee and Olson, 2013).…”

Section: Methodsmentioning

confidence: 99%

Computational study ofPiper betleL. phytocompounds byinsilico and ADMETanalysis for prediction of potential xanthine oxidase inhibitory activity

Periasamy

Muthusamy

Lakshmanan

et al. 2023

Preprint

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Background: Xanthine oxidase (XO) enzyme is directly associated with pathogenesis of gout and indirectly with cancer, diabetes and metabolic syndromes. Allopurinol is a xanthine oxidase inhibitor which is useful in the treatment of gout but it causes side effects in humans and birds. Therefore, this study sought to identify the alternative compound from the natural resources with fewer side effects than the conventional ones. Objectives: The present study was designed to find out the xanthine oxidase inhibitory activity of Piper betle phytocompounds in comparison with Allopurinol. Methods: The detection of phytocompounds present in the P. betle L. extract was identified through Gas Chromatography Mass Spectrometry (GC-MS) analysis. The insilico analysis and ADMET properties were evaluated for the GC-MS derived P. betle phytocompounds. Among the 32 phyto compounds of P. betle, 18 were showed favourable affinity with xanthine oxidase and their different conformational structures were docked in schrodinger module with xanthine oxidase enzyme structure. The interpretation of results was carried out through GLIDE XP Scoring, GLIDE Energy, MM-GBSA energy and hydrogen bond and PiPi interactions. Further the absorption, distribution, metabolism, excretion and toxicity (ADMET) analysis were also carried out using QIKPRO programme. Results: The results revealed that, the twelve phytocompounds of P. betle showed GLIDE XP docking score (- 6.881 to - 4.766 Kcal/mol) higher than allopurinol (- 4.535 Kcal/mol) and 11 phytocompounds showed higher GLIDE energy (- 42.822 Kcal/mol to - 36.706 Kcal/mol) than allopurinol (- 32.676 Kcal/mol). Chromonol and eugenol were the most potential compounds of P. betle which showed both hydrogen bond and Pi-Pi interactions with the target xanthine oxidase as that of standard drug allopurinol. The selected phytocompounds satisfied the ADME descriptors and have no violation of Lipinski's rule of five. Conclusions: The insilico and ADMET profile study on the phytocompounds of P. betle predicted their promising potential xanthine oxidase inhibition activity and they could be developed as alternate molecules against synthetic agents by invivo experiments for the treatment of xanthine oxidase associated diseases like hyperuricimia and cardiovascular disorders.

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Protease activated receptor-2 (PAR2): possible target of phytochemicals

Cited by 12 publications

References 80 publications

Novel ligand-based docking; molecular dynamic simulations; and absorption, distribution, metabolism, and excretion approach to analyzing potential acetylcholinesterase inhibitors for Alzheimer's disease

Novel ligand-based docking; molecular dynamic simulations; and absorption, distribution, metabolism, and excretion approach to analyzing potential acetylcholinesterase inhibitors for Alzheimer's disease

Molecular Docking and Molecular Dynamics Studies of Antidiabetic Phenolic Compound Isolated from Leaf Extract of Englerophytum magalismontanum (Sond.) T.D.Penn.

Computational study ofPiper betleL. phytocompounds byinsilico and ADMETanalysis for prediction of potential xanthine oxidase inhibitory activity

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