Virtual structure-based docking, WaterMap, and molecular dynamics guided identification of the potential natural compounds as inhibitors of protein-tyrosine phosphatase 1B

Current treatments for diabetes mellitus are ineffective, as evidenced by the rise in diabetes cases. This has forced researchers to develop novel chemicals as drugs to block the enzyme alpha-amylase as the severe way to treat diabetes disease. Many previous studies were done to determine the biological activity of a set of molecules isolated from medicinal plants. Morocco is renowned for the abundance of plants it has and for the traditional medical uses of these plants, which drives us to employ our cultural heritage and the variety of our nation's natural resources in the therapeutic area. In the current study, extensive research was conducted to compile a group of phytoconstituents derived from Moroccan plants and used in conventional Moroccan medicine to treat local illnesses. To assess the stability of the generated complexes, molecular docking of the investigated compounds was carried out in the active site of 4 distinct alpha-amylase proteins. The remaining compounds with a high negative binding affinity were then subjected to the ADMET analysis to determine their pharmacological characteristics. The findings showed that two drugs have strong binding affinity for the target proteins and may be used orally as potential alpha-amylase inhibitors. The results of molecular dynamics analysis and MMGBSA calculation were used to validate the optimal stability of created complexes (L97 with studied proteins 1HNY, 1OSE, 1UA7 and 1BAG).

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Structure‐Based Virtual Screening, ADMET analysis, and Molecular Dynamics Simulation of Moroccan Natural Compounds as Candidates α‐Amylase Inhibitors

Abchir

Yamari

Nour

et al. 2023

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Enamino Barbiturates as Antiproliferative and Antimicrobial Agents: Studies on Synthesis, Biological Activities, and Molecular Modeling

Shtaiwi,

Abu Sarhan,

Aljaar

et al. 2024

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In the present study, the aimed enamines 3 a–j were synthesized with yield ranging between 65 and 81 % by the reaction of 5‐((dimethylamino)methylene)‐1,3‐dimethylpyrimidine‐2,4,6(1H,3H,5H) ‐trione (2) with different amines at room temperature (25 °C). The structures of all synthesized compounds were characterized using different spectroscopic techniques. Molecular docking studies of the new compounds 3 a–j were carried out with human estrogen receptor (hER) enzyme to evaluate their activities as an effective drug molecules. It was investigated that the compounds 3 b, 3 e, 3 f and 3 j revealed the best binding affinities. All new compounds were evaluated towards antifungal activities, which conceded that the compound 3 e displayed a remarkable antifungal activity compared to the Fluconazole and Nystatin, and its Minimum Inhibitory Concentration (MIC) found to be 0.011 mM, while for Fluconazole the MIC value exhibited at 0.046 mM. Additionally, the toxicity for the new compounds found to be better than tamoxifen on MCF‐7 cells and among these molecules, the compound 3 e displayed the lowest IC50 value.

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Molecular dynamics and structure-based virtual screening and identification of natural compounds as Wnt signaling modulators: possible therapeutics for Alzheimer’s disease

et al. 2022

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Wnt signaling pathway is an evolutionarily conserved pathway responsible for neurogenesis, axon outgrowth, neuronal polarity, synapse formation, and maintenance. Downregulation of Wnt signaling has been found in patients with Alzheimer’s disease (AD). Several experimental approaches to activate Wnt signaling pathway have proven to be beneficial in alleviating AD, which is one of the new therapeutic approaches for AD. The current study focuses on the computational structure-based virtual screening followed by the identification of potential phytomolecules targeting different markers of Wnt signaling like WIF1, DKK1, LRP6, GSK-3β, and acetylcholine esterase. Initially, screening of 1924 compounds from the plant-based library of Zinc database was done for the selected five proteins using docking approach followed by MM-GBSA calculations. The top five hit molecules were identified for each protein. Based on docking score, and binding interactions, the top two hit molecules for each protein were selected as promising molecules for the molecular dynamic (MD) simulation study with the five proteins. Therefore, from this in silico based study, we report that Mangiferin could be a potential molecule targeting Wnt signaling pathway modulating the LRP6 activity, Baicalin for AChE activity, Chebulic acid for DKK1, ZINC103539689 for WIF1, and Morin for GSk-3β protein. However, further validation of the activity is warranted based on in vivo and in vitro experiments for better understanding and strong claim. This study provides an in silico approach for the identification of modulators of the Wnt signaling pathway as a new therapeutic approach for AD. Graphical Abstract

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Virtual structure-based docking, WaterMap, and molecular dynamics guided identification of the potential natural compounds as inhibitors of protein-tyrosine phosphatase 1B

Cited by 10 publications

References 15 publications

Structure‐Based Virtual Screening, ADMET analysis, and Molecular Dynamics Simulation of Moroccan Natural Compounds as Candidates α‐Amylase Inhibitors

Structure‐Based Virtual Screening, ADMET analysis, and Molecular Dynamics Simulation of Moroccan Natural Compounds as Candidates α‐Amylase Inhibitors

Enamino Barbiturates as Antiproliferative and Antimicrobial Agents: Studies on Synthesis, Biological Activities, and Molecular Modeling

Molecular dynamics and structure-based virtual screening and identification of natural compounds as Wnt signaling modulators: possible therapeutics for Alzheimer’s disease

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