Computational screening of benzophenone integrated derivatives (BIDs) targeting the NACHT domain of the potential target NLRP3 inflammasome

Patil, Shashank M.; Manu, G.; Shivachandra, Jagadeep Chandra; Kumar, Kuldeep; Vigneswaran, Jaanaky; Ramu, Ramith; Shirahatti, Prithvi S.; Ranganatha, V. Lakshmi

doi:10.1016/j.adcanc.2022.100056

Cited by 13 publications

(8 citation statements)

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“…Further, the compounds were screened based on their ADMET properties. To deduce the pharmacokinetic properties and their functions inside the body, the ADMET study was conducted based on previous works of the authors using ADMETlab 2.0 ( ) (accessed on 10 July 2022) [ 16 , 17 ].…”

Section: Methodsmentioning

confidence: 99%

Phyto-Computational Intervention of Diabetes Mellitus at Multiple Stages Using Isoeugenol from Ocimum tenuiflorum: A Combination of Pharmacokinetics and Molecular Modelling Approaches

et al. 2022

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In the present study, the anti-diabetic potential of Ocimum tenuiflorum was investigated using computational techniques for α-glucosidase, α-amylase, aldose reductase, and glycation at multiple stages. It aimed to elucidate the mechanism by which phytocompounds of O. tenuiflorum treat diabetes mellitus using concepts of druglikeness and pharmacokinetics, molecular docking simulations, molecular dynamics simulations, and binding free energy studies. Isoeugenol is a phenylpropene, propenyl-substituted guaiacol found in the essential oils of plants. During molecular docking modelling, isoeugenol was found to inhibit all the target enzymes, with a higher binding efficiency than standard drugs. Furthermore, molecular dynamic experiments revealed that isoeugenol was more stable in the binding pockets than the standard drugs used. Since our aim was to discover a single lead molecule with a higher binding efficiency and stability, isoeugenol was selected. In this context, our study stands in contrast to other computational studies that report on more than one compound, making it difficult to offer further analyses. To summarize, we recommend isoeugenol as a potential widely employed lead inhibitor of α-glucosidase, α-amylase, aldose reductase, and glycation based on the results of our in silico studies, therefore revealing a novel phytocompound for the effective treatment of hyperglycemia and diabetes mellitus.

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Section: Methodsmentioning

confidence: 99%

Phyto-Computational Intervention of Diabetes Mellitus at Multiple Stages Using Isoeugenol from Ocimum tenuiflorum: A Combination of Pharmacokinetics and Molecular Modelling Approaches

et al. 2022

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“…In addition to the docking, molecular dynamic (MD) simulation studies were performed to explain the dynamic behavior of the protein-ligand complex with respect to time under a solvated environment. The simulation study provides the analysis of protein-ligand complex RMSD, the Rg, SASA, ligand RMSD, the total number of ligand hydrogen bonds maintained throughout the simulation time, and the variation of secondary structure pattern between the protein and their complexes [ 37 , 38 ]. The RMSD of the protein-ligand complex depicts the stability of the same throughout the simulation by determining the presence of a ligand inside the binding pocket.…”

Section: Resultsmentioning

confidence: 99%

“…G Binding : binding free energy, G Complex : total free energy of the protein-ligand complex, G Protein and G Ligand : total free energies of the isolated protein and ligand in solvent, respectively, ΔG: standard free energy, ΔE MM : average molecular mechanics potential energy in vacuum, G Solvation : solvation energy, ΔE: total energy of bonded as well as non-bonded interactions, ΔS: change in entropy of the system upon ligand Binding, T: Temperature in Kelvin [ 36 , 37 ].…”

Section: Methodsmentioning

confidence: 99%

Integrated network pharmacology and molecular modeling approach for the discovery of novel potential MAPK3 inhibitors from whole green jackfruit flour targeting obesity-linked diabetes mellitus

et al. 2023

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The current study investigates the effectiveness of phytocompounds from the whole green jackfruit flour methanol extract (JME) against obesity-linked diabetes mellitus using integrated network pharmacology and molecular modeling approach. Through network pharmacology, druglikeness and pharmacokinetics, molecular docking simulations, GO analysis, molecular dynamics simulations, and binding free energy analyses, it aims to look into the mechanism of the JME phytocompounds in the amelioration of obesity-linked diabetes mellitus. There are 15 predicted genes corresponding to the 11 oral bioactive compounds of JME. The most important of these 15 genes was MAPK3. According to the network analysis, the insulin signaling pathway has been predicted to have the strongest affinity to MAPK3 protein, which was chosen as the target. With regard to the molecular docking simulation, the greatest notable binding affinity for MAPK3 was discovered to be caffeic acid (-8.0 kJ/mol), deoxysappanone B 7,3’-dimethyl ether acetate (DBDEA) (-8.2 kJ/mol), and syringic acid (-8.5 kJ/mol). All the compounds were found to be stable inside the inhibitor binding pocket of the enzyme during molecular dynamics simulation. During binding free energy calculation, all the compounds chiefly used Van der Waal’s free energy to bind with the target protein (caffeic acid: 102.296 kJ/mol, DBDEA: -104.268 kJ/mol, syringic acid: -100.171 kJ/mol). Based on these findings, it may be inferred that the reported JME phytocompounds could be used for in vitro and in vivo research, with the goal of targeting MAPK3 inhibition for the treatment of obesity-linked diabetes mellitus.

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“…The most used approach for calculating free binding energies has been determined as MM/PBSA. The binding free energy study demonstrates that van der Waal's energy and binding energy had an important impact in the development of protein-ligand complexes during MD simulation [106,107]. All hydroxycitric acid-free energy estimates were energetically viable.…”

Section: Binding Free Energy Calculationsmentioning

confidence: 95%

Antidiabetic Activity of Potential Probiotics Limosilactobacillus spp., Levilactobacillus spp., and Lacticaseibacillus spp. Isolated from Fermented Sugarcane Juice: A Comprehensive In Vitro and In Silico Study

Huligere

Alotaibi

et al. 2023

Nutrients

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Probiotics are regarded as a potential source of functional foods for improving the microbiota in human gut. When consumed, these bacteria can control the metabolism of biomolecules, which has numerous positive effects on health. Our objective was to identify a probiotic putative Lactobacillus spp. from fermented sugarcane juice that can prevent α-glucosidase and α-amylase from hydrolyzing carbohydrates. Isolates from fermented sugarcane juice were subjected to biochemical, molecular characterization (16S rRNA) and assessed for probiotic traits. Cell-free supernatant (CS) and extract (CE) and also intact cells (IC) were examined for the inhibitory effect on α-glucosidase and α-amylase. CS of the strain showed the highest inhibition and was subjected to a liquid chromatography–mass spectrometry (LCMS) analysis to determine the organic acid profile. The in silico approach was employed to assess organic acid stability and comprehend enzyme inhibitors’ impact. Nine isolates were retained for further investigation based on the preliminary biochemical evaluation. Limosilactobacillus spp., Levilactobacillus spp., and Lacticaseibacillus spp. were identified based on similarity > 95% in homology search (NCBI database). The strains had a higher survival rate (>98%) than gastric and intestinal fluids, also a high capacity for adhesion (hydrophobicity > 56%; aggregation > 80%; HT-29 cells > 54%; buccal epithelial cells > 54%). The hemolytic assay indicated that the isolates could be considered safe. The isolates’ derivatives inhibited enzymes to varying degrees, with α-glucosidase inhibition ranging from 21 to 85% and α-amylase inhibition from 18 to 75%, respectively. The CS of RAMULAB54 was profiled for organic acid that showed the abundance of hydroxycitric acid, citric acid, and lactic acid indicating their role in the observed inhibitory effects. The in silico approach has led us to understand that hydroxycitric acid has the ability to inhibit both the enzymes (α-glucosidase and α-amylase) effectively. Inhibiting these enzymes helps moderate postprandial hyperglycemia and regulates blood glucose levels. Due to their promising antidiabetic potential, these isolates can be used to enhance intestinal health.

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Computational screening of benzophenone integrated derivatives (BIDs) targeting the NACHT domain of the potential target NLRP3 inflammasome

Cited by 13 publications

References 47 publications

Phyto-Computational Intervention of Diabetes Mellitus at Multiple Stages Using Isoeugenol from Ocimum tenuiflorum: A Combination of Pharmacokinetics and Molecular Modelling Approaches

Phyto-Computational Intervention of Diabetes Mellitus at Multiple Stages Using Isoeugenol from Ocimum tenuiflorum: A Combination of Pharmacokinetics and Molecular Modelling Approaches

Integrated network pharmacology and molecular modeling approach for the discovery of novel potential MAPK3 inhibitors from whole green jackfruit flour targeting obesity-linked diabetes mellitus

Antidiabetic Activity of Potential Probiotics Limosilactobacillus spp., Levilactobacillus spp., and Lacticaseibacillus spp. Isolated from Fermented Sugarcane Juice: A Comprehensive In Vitro and In Silico Study

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