Dissecting molecular mechanisms underlying the inhibition of β-glucuronidase by alkaloids from Hibiscus trionum: Integrating in vitro and in silico perspectives

Kamel, Emadeldin M.; Alkhayl, Faris F.Aba; Alqhtani, Haifa A.; Bin-Jumah, May; Rudayni, Hassan A.; Lamsabhi, Al Mokhtar

doi:10.1016/j.compbiomed.2024.108969

Computers in Biology and Medicine

2024

DOI: 10.1016/j.compbiomed.2024.108969

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Dissecting molecular mechanisms underlying the inhibition of β-glucuronidase by alkaloids from Hibiscus trionum: Integrating in vitro and in silico perspectives

Emadeldin M. Kamel,

Faris F.Aba Alkhayl,

Haifa A. Alqhtani

et al.

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Cited by 6 publications

References 46 publications

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Investigation of the Inhibitory Activity of β‐Arbutin and its Analogues on Tyrosinase Based on Molecular Docking and Enzyme Inhibition Kinetics

Lv,

Yao,

Han

et al. 2024

Chemistry & Biodiversity

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β‐Arbutin, a natural glucoside hydroquinone derivative known for its skin‐whitening properties through tyrosinase inhibition in melanin synthesis, may pose potential risks of allergy and carcinogenicity due to the release of hydroquinone during use. This study explores the inhibitory effects of phenyl‐β‐D‐pyranoglucoside (compound 1), 4‐methoxyphenyl‐β‐D‐pyranoglucoside (compound 2), 4‐hydroxymethylphenyl‐β‐D‐pyranoglucoside (compound 3), and β‐arbutin (compound 4) on tyrosinase using enzyme kinetics, molecular docking, and molecular dynamics simulations. Results show compounds 1, 3, and 4 exhibit competitive inhibition, while compound 2 shows mixed inhibition. Docking analysis reveals phenyl rings of all compounds interact with the enzyme's active site, with compound 3 forming a metal bond with copper ions. MD simulations indicate high stability for compounds 2, 3, and 4, with compound 3 showing the lowest RMSD and compact Rg, suggesting stronger binding. Compound 1 is less stable and less inhibitory. These insights are valuable for designing effective tyrosinase inhibitors.

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Investigation of the Inhibitory Activity of β‐Arbutin and its Analogues on Tyrosinase Based on Molecular Docking and Enzyme Inhibition Kinetics

Lv,

Yao,

Han

et al. 2024

Chemistry & Biodiversity

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Molecular Insights Into β‐Glucuronidase Inhibition by Alhagi Graecorum Flavonoids: A Computational and Experimental Approach

Kamel,

Maodaa,

Al‐Shaebi

et al. 2024

ChemistryOpen

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In this study, we aimed to investigate the inhibitory mechanisms of β‐glucuronidase by flavonoids derived from Alhagi graecorum through both experimental and computational approaches. The activity of β‐glucuronidase was assessed using an in vitro enzyme inhibition assay, where myricetin and chrysoeriol were identified as potent inhibitors based on their low IC50 values. Kinetic studies were conducted to determine the inhibition type, revealing that both compounds exhibit noncompetitive inhibition of β‐glucuronidase‐catalyzed hydrolysis of PNPG. Molecular docking was employed to explore the binding affinities of the flavonoids, showing that myricetin formed the highest number of polar interactions with the enzyme. Additionally, molecular dynamics (MD) simulations were performed to evaluate the stability of the enzyme‐inhibitor complexes, demonstrating consistent trajectory behavior for both compounds, with significant energy stabilization. Interaction energy analyses highlighted the dominant role of electrostatic forces in myricetin′s inhibition mechanism, while Van der Waals forces were more prominent for chrysoeriol. The MM/PBSA method was used to calculate the binding free energies, with myricetin and chrysoeriol exhibiting the lowest values. Potential energy landscape analysis further revealed that β‐glucuronidase adopts a more closed conformation when bound to these inhibitors, limiting substrate access. These findings suggest that flavonoids from Alhagi graecorum hold promise for clinical applications, particularly in managing drug‐induced enteropathy.

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Unraveling the mechanism of carbonic anhydrase IX inhibition by alkaloids from Ruta chalepensis: A synergistic analysis of in vitro and in silico data

Alqhtani,

Othman,

Aba Alkhayl

et al. 2024

Biochemical and Biophysical Research Communications

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Dissecting molecular mechanisms underlying the inhibition of β-glucuronidase by alkaloids from Hibiscus trionum: Integrating in vitro and in silico perspectives

Cited by 6 publications

References 46 publications

Investigation of the Inhibitory Activity of β‐Arbutin and its Analogues on Tyrosinase Based on Molecular Docking and Enzyme Inhibition Kinetics

Investigation of the Inhibitory Activity of β‐Arbutin and its Analogues on Tyrosinase Based on Molecular Docking and Enzyme Inhibition Kinetics

Molecular Insights Into β‐Glucuronidase Inhibition by Alhagi Graecorum Flavonoids: A Computational and Experimental Approach

Unraveling the mechanism of carbonic anhydrase IX inhibition by alkaloids from Ruta chalepensis: A synergistic analysis of in vitro and in silico data

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