Non-target biotransformation enzymes as a target for triazole-zinc mixtures.

Autor: Jaklová Dytrtová J; Charles University, Faculty of Physical Education and Sport, Sport Sciences-Biomedical Department, José Martího 269/31, 162 52, Prague 6, Czech Republic. Electronic address: dytrtova@ftvs.cuni.cz., Bělonožníková K; Charles University, Faculty of Science, Department of Biochemistry, Hlavova 2030/8, 128 43, Prague 2, Czech Republic., Jakl M; Czech University of Life Sciences Prague, Faculty of Agrobiology, Food and Natural Resources, Department of Agroenvironmental Chemistry and Plant Nutrition, Kamýcká 129, 165 00, Prague, Suchdol, Czech Republic., Chmelík J; Charles University, Faculty of Science, Department of Biochemistry, Hlavova 2030/8, 128 43, Prague 2, Czech Republic; Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, 142 20, Prague 4, Czech Republic., Kovač I; Charles University, Faculty of Physical Education and Sport, Sport Sciences-Biomedical Department, José Martího 269/31, 162 52, Prague 6, Czech Republic; Charles University, Faculty of Science, Department of Analytical Chemistry, Hlavova 2030/8, 128 43, Prague 2, Czech Republic., Ryšlavá H; Charles University, Faculty of Science, Department of Biochemistry, Hlavova 2030/8, 128 43, Prague 2, Czech Republic.
Jazyk: angličtina
Zdroj: Chemico-biological interactions [Chem Biol Interact] 2023 Sep 01; Vol. 382, pp. 110625. Date of Electronic Publication: 2023 Jul 06.
DOI: 10.1016/j.cbi.2023.110625
Abstrakt: Triazoles inhibit lanosterol 14α-demethylase and block ergosterol biosynthesis in fungal pathogens. However, they also interact with other cytochrome P450 enzymes and influence non-target metabolic pathways. Disturbingly, triazoles may interact with essential elements. The interaction of penconazole (Pen), cyproconazole (Cyp) and tebuconazole (Teb) with Zn 2+ results in the formation of deprotonated ligands in their complexes or in the creation of complexes with Cl - as a counterion or doubly charged complexes. Triazoles, as well as their equimolar cocktails with Zn 2+ (10 -6  mol/L), decreased the activities of the non-target enzymes CYP19A1 and CYP3A4. Pen most decreased CYP19A1 activity and was best bound to its active centre to block the catalytic cycle in computational analysis. For CYP3A4, Teb was found to be the most effective inhibitor by both, activity assay and interaction with the active centre. Teb/Cyp/Zn 2+ and Teb/Pen/Cyp/Zn 2+ cocktails also decreased the CYP19A1 activity, which was in correlation with the formation of numerous triazole-Zn 2+ complexes.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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