The anti-SARS-CoV-2 activity of novel 9, 10-dihydrophenanthrene derivatives: an insight into molecular docking, ADMET analysis, and molecular dynamics simulation

Yamari, Imane; Abchir, Oussama; Mali, Suraj N.; Errougui, Abdelkbir; Talbi, Mohamed; Kouali, M’hammed El; Chtita, Samir

doi:10.1016/j.sciaf.2023.e01754

Cited by 18 publications

(4 citation statements)

References 28 publications

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“…We used the PaDEL descriptor tool kit was used to compute a variety of descriptors, including topological, auto-correlation, fragment count, and geometrical descriptors. 39 , 40 To enhance the accuracy of these descriptors, we performed a manual pretreatment process to remove redundant descriptors. 41 Furthermore, we used the Kennard-Stone data preprocessing tool and a standard variance threshold of 0.001 to remove constant descriptors, and a coefficient threshold of 0.8 to eliminate highly correlated descriptors.…”

Section: Methodsmentioning

confidence: 99%

Ligand based-design of potential schistosomiasis inhibitors through QSAR, homology modeling, molecular dynamics, pharmacokinetics, and DFT studies

Ja'afaru,

Uzairu,

Chandra

et al. 2024

Journal of Taibah University Medical Sciences

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Section: Methodsmentioning

confidence: 99%

Ligand based-design of potential schistosomiasis inhibitors through QSAR, homology modeling, molecular dynamics, pharmacokinetics, and DFT studies

Ja'afaru,

Uzairu,

Chandra

et al. 2024

Journal of Taibah University Medical Sciences

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“…Previous studies on medicinal plants have described ligand pocket areas as the leading framework for figuring out the target protein active sites of drugs derived from plants efficiently [ 28 ]. Mainly, the docking protocol proceeds via a crucial path for highly effective results [ 29 ]. Consequently, the flavonoids detected in the LPE, diosmin (Lig I), biochanin A (Lig II), hesperidin (Lig III), quercetin (Lig IV), and hesperetin (Lig V) were subjected to docking simulation using the Autodock Vina [ 30 , 31 ] software (version 4.2) for its dominant capacity for docking all studied phenolic compounds at the same time under comparable conditions.…”

Section: Methodsmentioning

confidence: 99%

The Synergistic Influence of Polyflavonoids from Citrus aurantifolia on Diabetes Treatment and Their Modulation of the PI3K/AKT/FOXO1 Signaling Pathways: Molecular Docking Analyses and In Vivo Investigations

Hassan,

Elmageed,

El-Qazaz

et al. 2023

Pharmaceutics

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This study was aimed at probing the modulatory influence of polyflavonoids extracted from Citrus aurantifolia, lemon peel extract (LPE-polyflavonoids), on attenuating diabetes mellitus (DM) and its complications. HPLC investigations of the LPE exhibited the incidence of five flavonoids, including diosmin, biochanin A, hesperidin, quercetin, and hesperetin. The in silico impact on ligand-phosphatidylinositol 3-kinase (PI3K) interaction was investigated in terms of polyflavonoid class to explore the non-covalent intakes and binding affinity to the known protein active site. The drug likeness properties and pharmacokinetic parameters of the LPE-polyflavonoids were investigated to assess their bioavailability in relation to Myricetin as a control. Remarkably, the molecular docking studies demonstrated a prominent affinity score of all these agents together with PI3K, implying the potency of the extract to orchestrate PI3K, which is the predominant signal for lessening the level of blood glucose. To verify these findings, in vivo studies were conducted, utilizing diabetic male albino rats treated with LPE-polyflavonoids and other groups treated with hesperidin and diosmin as single flavonoids. Our findings demonstrated that the LPE-polyflavonoids significantly ameliorated the levels of glucose, insulin, glycogen, liver function, carbohydrate metabolizing enzymes, G6Pd, and AGEs compared to the diabetic rats and those exposed to hesperidin and diosmin. Furthermore, the LPE-polyflavonoids regulated the TBARS, GSH, CAT, TNF-α, IL-1β, IL-6, and AFP levels in the pancreatic and hepatic tissues, suggesting their antioxidant and anti-inflammatory properties. In addition, the pancreatic and hepatic GLUT4 and GLUT2 were noticeably increased in addition to the pancreatic p-AKT in the rats administered with the LPE-polyflavonoids compared to the other diabetic rats. Remarkably, the administration of LPE-polyflavonoids upregulated the expression of the pancreatic and hepatic PI3K, AMPK, and FOXO1 genes, emphasizing the efficiency of the LPE in orchestrating all the signaling pathways necessitated to reduce the diabetes mellitus. Notably, the histopathological examinations of the pancreatic and hepatic tissues corroborated the biochemical results. Altogether, our findings accentuated the potential therapeutic role of LPE-polyflavonoids in controlling diabetes mellitus.

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“…The molecular dynamics technique is of important value in many drug discovery studies, including but not limited to the discovery of novel cures for emerging diseases, the characterization of the behavioral nature of macromolecules, the interpretation of amino acid mutations on drug resistance cases and the predictive estimation of the strength of binding between the drugs and their targets [63,64]. The last one was our primary goal from the molecular dynamic simulations in addition to the validation of the docking results retrieved from the docking process.…”

Section: Molecular Dynamicsmentioning

confidence: 99%

DFT and molecular simulation validation of the binding activity of PDEδ inhibitors for repression of oncogenic k-Ras

Majrashi,

Sabt,

Almahli

et al. 2024

PLoS ONE

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The development of effective drugs targeting the K-Ras oncogene product is a significant focus in anticancer drug development. Despite the lack of successful Ras signaling inhibitors, recent research has identified PDEδ, a KRAS transporter, as a potential target for inhibiting the oncogenic KRAS signaling pathway. This study aims to investigate the interactions between eight K-Ras inhibitors (deltarazine, deltaflexin 1 and 2, and its analogues) and PDEδ to understand their binding modes. The research will utilize computational techniques such as density functional theory (DFT) and molecular electrostatic surface potential (MESP), molecular docking, binding site analyses, molecular dynamic (MD) simulations, electronic structure computations, and predictions of the binding free energy. Molecular dynamic simulations (MD) will be used to predict the binding conformations and pharmacophoric features in the active site of PDEδ for the examined structures. The binding free energies determined using the MMPB(GB)SA method will be compared with the observed potency values of the tested compounds. This computational approach aims to enhance understanding of the PDEδ selective mechanism, which could contribute to the development of novel selective inhibitors for K-Ras signaling.

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The anti-SARS-CoV-2 activity of novel 9, 10-dihydrophenanthrene derivatives: an insight into molecular docking, ADMET analysis, and molecular dynamics simulation

Cited by 18 publications

References 28 publications

Ligand based-design of potential schistosomiasis inhibitors through QSAR, homology modeling, molecular dynamics, pharmacokinetics, and DFT studies

Ligand based-design of potential schistosomiasis inhibitors through QSAR, homology modeling, molecular dynamics, pharmacokinetics, and DFT studies

The Synergistic Influence of Polyflavonoids from Citrus aurantifolia on Diabetes Treatment and Their Modulation of the PI3K/AKT/FOXO1 Signaling Pathways: Molecular Docking Analyses and In Vivo Investigations

DFT and molecular simulation validation of the binding activity of PDEδ inhibitors for repression of oncogenic k-Ras

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