Unveiling the tyrosinase inhibitory potential of phenolics from Centaurium spicatum: Bridging in silico and in vitro perspectives

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 147, P. 107397 - 107397

Published: April 25, 2024

Language: Английский

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Deciphering the Molecular Mechanisms of Reactive Metabolite Formation in the Mechanism-Based Inactivation of Cytochrome p450 1B1 by 8-Methoxypsoralen and Assessing the Driving Effect of phe268

Molecules, Journal Year: 2024, Volume and Issue: 29(7), P. 1433 - 1433

Published: March 22, 2024

This study provides a comprehensive computational exploration of the inhibitory activity and metabolic pathways 8-methoxypsoralen (8-MP), furocoumarin derivative used for treating various skin disorders, on cytochrome P450 (P450). Employing quantum chemical DFT calculations, molecular docking, dynamics (MD) simulations analyses, biotransformation mechanisms active site binding profile 8-MP in CYP1B1 were investigated. Three plausible inactivation minutely scrutinized. Further analysis explored formation reactive metabolites subsequent processes, including covalent adduct through nucleophilic addition to epoxide, epoxide hydrolysis, non-CYP-catalyzed ring opening. Special attention was paid catalytic effect residue Phe268 mechanism-based (MBI) by 8-MP. Energetic profiles facilitating conditions revealed slight preference C4′=C5′ epoxidation pathway, while recognizing potential kinetic competition with 8-OMe demethylation pathway due comparable energy demands. The adducts via addition, particularly phenylalanine, generation potentially harmful autocatalyzed cleavage are likely contribute significantly metabolism Our findings highlight key role retaining within CYP1B1, thereby initial oxygen transition states. research offers crucial molecular-level insights that may guide early stages drug discovery risk assessment related use

Language: Английский

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Deciphering molecular mechanisms underlying the inhibition of β-glucuronidase by xanthones from Centaurium spicatum

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 150, P. 107609 - 107609

Published: July 2, 2024

Language: Английский

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Mechanistic insights into alkaloid-based inhibition of squalene epoxidase: A combined in silico and experimental approach for targeting cholesterol biosynthesis

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

Published: Feb. 1, 2025

Language: Английский

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Multi-pronged molecular insights into flavonoid-mediated inhibition of squalene epoxidase: a pathway to novel therapeutics

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

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Phytochemical Inhibitors of Squalene Epoxidase: Integrated In silico and In vitro Mechanistic Insights for Targeting Cholesterol Biosynthesis

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

Published: March 5, 2025

Language: Английский

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Bridging in silico and in vitro perspectives to unravel molecular mechanisms underlying the inhibition of β-glucuronidase by coumarins from Hibiscus trionum

Biophysical Chemistry, Journal Year: 2024, Volume and Issue: 313, P. 107304 - 107304

Published: July 26, 2024

Language: Английский

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Mechanistic insights into the metabolic pathways of vanillin: unraveling cytochrome P450 interaction mechanisms and implications for food safety

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

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Unraveling molecular mechanisms of β-glucuronidase inhibition by flavonoids from Centaurea scoparia: integrated in silico and in vitro insights

New Journal of Chemistry, Journal Year: 2024, Volume and Issue: 48(32), P. 14236 - 14252

Published: Jan. 1, 2024

Investigating the detailed molecular mechanisms of β-glucuronidase inhibition is critical for pioneering new therapeutic solutions and driving progress in pharmaceutical research.

Language: Английский

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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

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

Published: Sept. 11, 2024

Language: Английский

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