Molecular Insights Into β‐Glucuronidase Inhibition by Alhagi Graecorum Flavonoids: A Computational and Experimental Approach DOI Creative Commons
Emadeldin M. Kamel, Saleh N. Maodaa, Esam M. Al‐Shaebi

et al.

ChemistryOpen, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 19, 2024

Abstract 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 was assessed using an in vitro enzyme inhibition assay, where myricetin chrysoeriol were identified as potent inhibitors based on their low IC 50 values. Kinetic studies conducted determine type, revealing that compounds exhibit noncompetitive β‐glucuronidase‐catalyzed hydrolysis PNPG. Molecular docking employed explore binding affinities flavonoids, showing formed highest number polar interactions with enzyme. Additionally, molecular dynamics (MD) simulations performed evaluate stability enzyme‐inhibitor complexes, demonstrating consistent trajectory behavior for compounds, significant energy stabilization. Interaction analyses highlighted dominant role electrostatic forces myricetin′s mechanism, while Van der Waals more prominent chrysoeriol. MM/PBSA method used calculate free energies, exhibiting lowest Potential landscape analysis further revealed adopts a closed conformation when bound these inhibitors, limiting substrate access. These findings suggest hold promise clinical applications, particularly managing drug‐induced enteropathy.

Language: Английский

Mechanistic insights into alkaloid-based inhibition of squalene epoxidase: A combined in silico and experimental approach for targeting cholesterol biosynthesis DOI
Emadeldin M. Kamel,

Sarah I. Othman,

Faris F. Aba Alkhayl

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 140609 - 140609

Published: Feb. 1, 2025

Language: Английский

Citations

7
Multi-pronged molecular insights into flavonoid-mediated inhibition of squalene epoxidase: a pathway to novel therapeutics DOI Creative Commons
Emadeldin M. Kamel,

Sarah I. Othman,

Hassan A. Rudayni

et al.

RSC Advances, Journal Year: 2025, Volume and Issue: 15(5), P. 3829 - 3848

Published: Jan. 1, 2025

Apigenin-7-O-glucoside, silibinin, and baicalin are potent squalene epoxidase inhibitors with promising therapeutic potential. Integrative in silico experimental studies pave the way for hypercholesterolemia antifungal therapies.

Language: Английский

Citations

7
Inhibitory Mechanisms of β‐Glucuronidase by Hibiscus syriacus Phenolics: Integrating Computational and Experimental Approaches DOI Open Access
Haifa A. Alqhtani,

Sarah I. Othman,

Faris F. Aba Alkhayl

et al.

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 1, 2025

Abstract Exploring the intricate mechanisms of β ‐glucuronidase inhibition is essential to advancing development novel therapeutic agents. This study extensively evaluated inhibitory potential phenolics from Hibiscus syriacus against using a combination in vitro and computational approaches. assays demonstrated that chlorogenic acid dactylifric exhibited significant activity, with low IC 50 values 1.32 ± 0.08 10.02 1.38 µM, respectively. Enzyme kinetics analyses revealed positive control, EGCG, followed mixed mechanism, while displayed competitive inhibition, as indicated by intersecting lines Lineweaver–Burk plots. Docking studies supported these findings, showing lowest binding affinities, extensive polar interactions, occupancy identical sites reference drug. A 30 ns molecular dynamics simulation was performed explore interaction between isolated phenolic compounds ‐glucuronidase. Evaluation multiple MD parameters stable trajectories substantial energy stabilization their These findings are consistent experimental data, supporting inhibitors

Language: Английский

Citations

5
Phytochemical Inhibitors of Squalene Epoxidase: Integrated In silico and In vitro Mechanistic Insights for Targeting Cholesterol Biosynthesis DOI
Emadeldin M. Kamel,

Doaa A. Abdelrheem,

Bashir Salah

et al.

Archives of Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: 768, P. 110372 - 110372

Published: March 5, 2025

Language: Английский

Citations

5
Mechanistic insights into the metabolic pathways of vanillin: unraveling cytochrome P450 interaction mechanisms and implications for food safety DOI
Emadeldin M. Kamel, Saleh N. Maodaa, Esam M. Al‐Shaebi

et al.

Organic & Biomolecular Chemistry, Journal Year: 2024, Volume and Issue: 22(32), P. 6561 - 6574

Published: Jan. 1, 2024

Vanillin, a key flavor compound found in vanilla beans, is widely used the food and pharmaceutical industries for its aromatic properties potential therapeutic benefits. This study presents comprehensive quantum chemical analysis to elucidate interaction mechanisms of vanillin with CYP450 enzymes, focus on mechanism-based inactivation. Three inactivation pathways were evaluated: aldehyde deformylation, methoxy dealkylation, acetal formation. Aldehyde deformylation was identified as most energy-efficient, involving removal group from leading formation benzyne intermediates that could react iron porphyrin moiety CYP450, potentially resulting enzyme Further investigation into interactions CYP2E1 CYP1A2 conducted using molecular docking dynamics (MD) simulation. The analyses supported findings DFT studies, wherein revealed high binding affinities studied isozymes. Moreover, occupied main site both isozymes, evidenced by inclusion heme their mechanisms. Employing 100 ns simulation, we scrutinized between two isozymes CYP450. assessment various MD parameters along energies exhibited stable trajectories substantial energy stabilization during These insights can guide future research ensure safe application vanillin, especially scenarios where it may interact enzymes.

Language: Английский

Citations

14
Unraveling the Mechanism of Carbonic Anhydrase IX Inhibition by Alkaloids from Ruta chalepensis: A Synergistic Analysis of In Vitro and In Silico Data DOI
Haifa A. Alqhtani,

Sarah I. Othman,

Faris F. Aba Alkhayl

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 733, P. 150685 - 150685

Published: Sept. 11, 2024

Language: Английский

Citations

11
Dynamic interactions and inhibitory mechanisms of Artemisia annua terpenoids with carbonic anhydrase IX DOI Creative Commons
Emadeldin M. Kamel, Faris F. Aba Alkhayl, Haifa A. Alqhtani

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: unknown, P. 136982 - 136982

Published: Oct. 1, 2024

Language: Английский

Citations

10
Integrating Computational Modeling and Experimental Validation to Unveil Tyrosinase Inhibition Mechanisms of Flavonoids from Alhagi graecorum DOI Creative Commons
Reem S. Alruhaimi, Ayman M. Mahmoud, Sulaiman Mohammed Alnasser

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: 9(47), P. 47167 - 47179

Published: Nov. 13, 2024

Flavonoids, natural compounds ubiquitous in the human diet, are esteemed for their multifaceted pharmacological properties. The tyrosinase inhibitory capacity of five flavonoids from Alhagi graecorum was investigated through a comprehensive integration vitro and silico methodologies. Molecular docking simulations demonstrated proficient binding isolated to principal site tyrosinase, akin standard inhibitor kojic acid. These exhibited analogous affinities, among which compound 5 manifested notably heightened levels polar bonds hydrophobic interactions. dynamics (MD) were utilized explore interaction between tyrosinase. analysis various MD parameters revealed consistent trajectories tested compounds, with demonstrating notable energy equilibration. Strong hydrogen bonding interactions observed active site. results calculations showed balanced mediated by interactions, exhibiting lowest energies. Additionally, findings MM/PBSA free 5. Moreover, inhibition assay discrepancies studied flavonoids. Particularly, most pronounced anti-tyrosinase activity, as evidenced its IC50 value. This experimental outcome is computational predictions. Therefore, A. might be valuable development inhibitors.

Language: Английский

Citations

5
De novo in silico screening of natural products for antidiabetic drug discovery: ADMET profiling, molecular docking, and molecular dynamics simulations DOI
Sulyman Olalekan Ibrahim, Yusuf Oloruntoyin Ayipo, Halimat Yusuf Lukman

et al.

In Silico Pharmacology, Journal Year: 2025, Volume and Issue: 13(1)

Published: Feb. 17, 2025

Language: Английский

Citations

0
Molecular Modeling Studies of Hapten Design and Antibody Recognition for Sensitive Detection of Vitamin K3 by Strip Biosensor DOI
Jialin Hu, Xinxin Xu, Liqiang Liu

et al.

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Abstract Computer‐aided molecular design techniques are used to analyze vitamin K3 (VK3) and VK3‐hapten. Based on VK3‐hapten, a specific monoclonal antibody (mAb) against VK3 is prepared with sensitivity (IC 50 ) of 0.49 ng mL −1 . The recombinant technology investigate the docking mechanism mAb recognition VK3. Then, model established, amino acid distributions complementarity determining region regions determined. Hydrogen bonding hydrophobic interactions acids further confirmed by these results, gold immunochromatographic assay (GICA) developed detect recovery in sample 99.50%–101.12%, showing better agreement results high‐performance liquid chromatography. In addition, calculated limit detection milk powder, tablets, mixed animal feed 1.16, 1.18, 10.06 µg kg , respectively. concentrations tablets as determined GICA strips 5.82 mg/tablet 1.47 mg These that have great potential for detecting actual samples.

Language: Английский

Citations

0