How Plant Polyhydroxy Flavonoids Can Hinder the Metabolism of Cytochrome 3A4 DOI Creative Commons
Carina Vieira, Marisa Freitas, Andreia Palmeira

и другие.

Biomedicines, Год журнала: 2025, Номер 13(3), С. 655 - 655

Опубликована: Март 7, 2025

Background/Objectives: Recent interest in dietary components and their effects on xenobiotic metabolism has highlighted role modulating drug pharmacokinetics. Cytochrome P450 3A4, a key isoform of the cytochrome superfamily, is involved over 50% xenobiotics. Flavonoids, present various foods supplements, exhibit diverse biological activities influenced by structural modifications scaffold. Methods: Fifteen polyhydroxy-flavonoid compounds were firstly tested high-throughput fluorimetric method for ability to inhibit CYP3A4, where scutellarein gossypetin assessed first time. A molecular docking analysis was performed most active inhibitors gain insight interaction with site enzyme. Results: Baicalein, luteolin, potent flavones, presenting an IC50 15 ± 5, 31 10, 19 7 μmol/L, respectively. Gossypetin, herbacetin, quercetin flavonols 40 8, 32 23 5 The showed that hydroxyl groups at C6, C7, C8 (ring A), C3’ B) flavone structure affect CYP3A4 enzyme catalysis binding its substrate-binding as strong known antiviral antifungal drugs. Conclusions: Binding enzyme’s strength comparable drugs, baicalein identified flavonoids. vicinal hydroxyls those molecules pivotal positioning stabilization catalytic pocket.

Язык: Английский

How Plant Polyhydroxy Flavonoids Can Hinder the Metabolism of Cytochrome 3A4 DOI Creative Commons
Carina Vieira, Marisa Freitas, Andreia Palmeira

и другие.

Biomedicines, Год журнала: 2025, Номер 13(3), С. 655 - 655

Опубликована: Март 7, 2025

Background/Objectives: Recent interest in dietary components and their effects on xenobiotic metabolism has highlighted role modulating drug pharmacokinetics. Cytochrome P450 3A4, a key isoform of the cytochrome superfamily, is involved over 50% xenobiotics. Flavonoids, present various foods supplements, exhibit diverse biological activities influenced by structural modifications scaffold. Methods: Fifteen polyhydroxy-flavonoid compounds were firstly tested high-throughput fluorimetric method for ability to inhibit CYP3A4, where scutellarein gossypetin assessed first time. A molecular docking analysis was performed most active inhibitors gain insight interaction with site enzyme. Results: Baicalein, luteolin, potent flavones, presenting an IC50 15 ± 5, 31 10, 19 7 μmol/L, respectively. Gossypetin, herbacetin, quercetin flavonols 40 8, 32 23 5 The showed that hydroxyl groups at C6, C7, C8 (ring A), C3’ B) flavone structure affect CYP3A4 enzyme catalysis binding its substrate-binding as strong known antiviral antifungal drugs. Conclusions: Binding enzyme’s strength comparable drugs, baicalein identified flavonoids. vicinal hydroxyls those molecules pivotal positioning stabilization catalytic pocket.

Язык: Английский

Процитировано

0