Exploring the Protein Tyrosine Phosphatase 1B Inhibitory Potentials of Naturally Occurring Brazilin-Type Homoisoflavonoids: A Computational Approach

Awotuya, Iyanu O.; Fakola, Emmanuel G.; Olusola, Ayobami J.; Olanudun, Esther A.; Bello, Oyenike Idayat; Ogunremi, Bioluwatife I.; Gboyero, Felix Olusegun; Adesida, Stephen A; Faloye, Kolade Olatubosun

doi:10.1007/s42250-022-00415-3

Cited by 5 publications

(5 citation statements)

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Quantum parameters such as ionization energy (I), electron affinity (A), chemical hardness (η), electronic chemical potential (µ), and electronegativity (χ) were computed from the frontier molecular orbital energies using the following relationships as presented in Equations ( 1) to ( 7). [37][38][39][40] Energy gap…”

Section: Dft Calculationsmentioning

confidence: 99%

“…To validate the docking protocol, the co-crystallized ligand was re-docked into the binding pocket of 6LU7 using PyRx 0.840, and the RMSD value between the co-crystallized ligand and the re-docked ligand was computed. 40 Ligand modelling. A total of 10 hydrazones and 1 hydrazide were generated using ChemDraw software, and their 3D structures were obtained using Chem-3D.…”

Section: Molecular Dockingmentioning

confidence: 99%

“…The ligand structures underwent energy minimization using the MMF94x force field in the PyRx 0.8 tool, specifically the Open Babel plugin tool and were subsequently saved in PDB format for subsequent docking analyses. 40 To carry out molecular docking, the energy of the compounds was minimized under MMFF94x force field employing the steepest descent method for 200 steps with a step size of 0.02 and converted from PDB open babel programme in PyRx 0.8 software. Next, the grid box size was set at 25 Å and centre at X = −25.9959 Å, Y = 12.5892 Å, and Z = 59.1535 Å for the main protease (Mpro).…”

Section: Molecular Dockingmentioning

confidence: 99%

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Investigation of Methyl-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxyhydrazide Derivatives as Potential Inhibitors of COVID-19 Main Protease: DFT and Molecular Docking Study

Akinyele,

Fakola,

Adeboye

et al. 2023

Bioinform Biol Insights

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The search for effective therapeutics to combat COVID-19 has led to the exploration of the biological activity of numerous compounds. In this study, hydrazones derived from oseltamivir intermediate, methyl 5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylate have been investigated for their potential as drug candidates against the COVID-19 virus using computational methods, including density functional theory (DFT) studies, molecular docking, and absorption, distribution, metabolism, excretion and toxicity (ADMET) analysis. The DFT studies provide information on the electronic properties of the compounds while the molecular docking results using AutoDock reported the binding energies between the main protease of COVID-19 and the compounds. The DFT results revealed that the energy gap of the compounds ranged from 4.32 to 5.82 eV while compound HC had the highest energy gap (5.82 eV) and chemical potential (2.90 eV). The electrophilicity index values of the 11 compounds ranged from 2.49 to 3.86, thus they were classified as strong electrophiles. The molecular electrostatic potential (MESP) revealed electron-rich and electron-deficient regions of the compounds. The docking results reveal that all the compounds had better docking scores than remdesivir and chloroquine, frontline drugs employed in combating COVID-19, with HC having the best docking score of -6.5. The results were visualized using Discovery studio, which revealed hydrogen bonding, pi-alkyl interaction, alkyl interaction, salt bridge interaction, halogen interaction as being responsible for the docking scores. The drug-likeness results showed that the compounds qualify as oral drug candidates as none of them violated Vebers and Lipinski’s rule. Thus, they could serve as potential inhibitors of COVID-19.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%