BioNanoScience, Journal Year: 2024, Volume and Issue: 14(3), P. 2930 - 2939
Published: July 12, 2024
Language: Английский
Scientific African, Journal Year: 2025, Volume and Issue: unknown, P. e02567 - e02567
Published: Feb. 1, 2025
Language: Английский
Citations
1
Bioelectrochemistry, Journal Year: 2025, Volume and Issue: 163, P. 108913 - 108913
Published: Jan. 22, 2025
The ability of the living world to flourish in face constant exposure dangerous chemicals depends on management a widespread group enzymes known as heme-thiolate monooxygenases or cytochrome P450 superfamily. About three-quarters all reactions determining metabolism endogenous compounds, those carried foods, taken drugs, even synthetic discarded into environment depend their catalytic performance. chromatographic and (photo)luminometric methods routinely used predictive analytical tools laboratories have significant drawbacks ranging from limited shelf-life reagents, use substrates, laborious tedious procedures for highly sensitive detection. In this review, alternative electrochemical biosensors using bio-element are emphasized main aspects well regarding implementation usefulness. Despite various schemes proposed implementation, reports real applications scant several reasons, including low reaction rates, broad substrate specificity, uncoupling occurrence, need expensive electron transfer partners promote transfer. Finally, prospect future developments is introduced, focusing integrating miniaturized systems with techniques, alongside optimizing enzyme immobilization electrode modifications improve enzymatic stability enhance sensor reliability. This progress represents crucial step towards creation portable that mimic human physiological responses, supporting precision medicine approach.
Language: Английский
Citations
0
Published: March 22, 2025
Introduction. Metabolic activation of xenobiotics, including pharma drugs, is considered to be one the main mechanisms for development idiosyncratic reactions. Accordingly, potential bioactivation a xenobiotic should carefully evaluated in early stages drug development. In this regard, search new rapid and effective screening techniques reactive metabolites xenobiotics presents particular interest. Objective . Development technique modeling processes biotransformation vitro identify indapamide. Materials methods Non-enzymatic instrumental methods, such as electrochemical oxidation (ECO) photocatalytic (PCO) volume, were used comparison methods. The second phase metabolism was modeled by incubating products indapamide with trapping agent (glutathione, GSH). products, well their conjugates GSH, then analyzed high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS). developed one-pot based on UV-induced PCO presence GSH surface target functionalized titanium dioxide followed detection matrix-assisted laser desorption/ionization (MALDI). Results. use ECO resulted 5 3 adducts while volume allowed 7 1 adduct GSH. detected 8 addition number known total 4 previously unstudied each three Conclusions. proposed analytical showed its higher informativity combined simplicity rapidity, which makes it promising candidate preclinical studies drugs predicting toxicity pharmaceutical objects, studying various xenobiotics.
Language: Английский
Citations
0
Published: March 29, 2024
In this article we introduce a proof of concept strategy: Computational Predictive and Electrochemical Detection Metabolites (CP-EDM) to expedite the discovery drug metabolites. The use bioactive natural product, piperine, that has well curated metabolite profile but an unpredictable computational metabolism (Biotransformer v3.0) was selected. We developed electrochemical reaction oxidise piperine into range metabolites, which were detected by LC-MS. turn, series chemically plausible metabolites predicted based on ion-fragmentation patterns. These docked active site CYP3A4 using Autodock4.2 From clustered low-energy in it can be inferred most likely metabolic position (based intermolecular distances Fe-oxo site) is benzo[d][1,3]dioxole motif. confirmed literature comparison delivered vide infra. Thus, demonstrating power hyphenated technique tandem detection evaluation binding poses. Taken together, outline novel approach where diverse data sources are combined predict confirm outcome for structure.
Language: Английский
Citations
2
Molecules, Journal Year: 2024, Volume and Issue: 29(10), P. 2406 - 2406
Published: May 20, 2024
In this article, we introduce a proof-of-concept strategy, Computational Predictive and Electrochemical Detection of Metabolites (CP-EDM), to expedite the discovery drug metabolites. The use bioactive natural product, piperine, that has well-curated metabolite profile but an unpredictable computational metabolism (Biotransformer v3.0) was selected. We developed electrochemical reaction oxidize piperine into range metabolites, which were detected by LC-MS. A series chemically plausible metabolites predicted based on ion fragmentation patterns. These docked active site CYP3A4 using Autodock4.2. From clustered low-energy in site, it can be inferred most likely metabolic position (based intermolecular distances Fe-oxo site) is benzo[d][1,3]dioxole motif. confirmed comparison with literature, delivered vide infra, thus, demonstrating power hyphenated technique tandem detection evaluation binding poses. Taken together, outline novel approach where diverse data sources are combined predict confirm outcome for structure.
Language: Английский
Citations
2
Molecules, Journal Year: 2024, Volume and Issue: 29(15), P. 3455 - 3455
Published: July 23, 2024
With the help of electrochemical methods, including CV and EIS, influence methimazole, carbimazole, concentration supporting electrolyte on kinetics mechanism zinc electroreduction a mercury electrode was compared analyzed. Moreover, molecular dynamics simulations zinc/carbimazole zinc/methimazole solutions were carried out to determine effect drugs hydration sphere Zn
Language: Английский
Citations
2
Analytical Chemistry, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 3, 2024
Electrochemistry offers an effective means of mimicking enzymatic metabolic pathways, particularly the oxidative pathways catalyzed by cytochrome P450 superfamily. The electrochemical generation and identification metabolites are time-sensitive, necessitating adjustable cell designs for accurate mechanistic interpretation. We present a thin-layer electrode (TLE) that addresses needs both analytical synthetic drug metabolites. TLE's ability to conduct experiments on minute-to-hour time scale allows detailed observation reaction mechanisms not easily identified traditional methods. utility TLE was benchmarked oxidation acetaminophen, acebutolol, 2-acetyl-4-butyramidophenol, known produce quinone imine metabolites, i.e., NAPQI, upon oxidation. When combined with microelectrode (μE), enables probing concentration profiles these drugs. micromole pipette-type structure facilitate comprehensive structural elucidation intermediates products using chromatographic spectroscopic techniques.
Language: Английский
Citations
2
Biomedical Chemistry Research and Methods, Journal Year: 2024, Volume and Issue: 7(1), P. e00210 - e00210
Published: Jan. 1, 2024
This article describes the approaches developed by authors with aim to increase efficiency of electro enzymatic reactions catalyzed cytochrome P450 3A4. A comparative analysis 3A4 systems was carried out during formation functional complexes hemoprotein-flavin nucleotides as low-molecular models NAD(P)H-dependent reductase. The a productive enzyme-substrate complex before stage ofaccepting electrons from modified electrode studied electocatalytic viewpoint. Incorporation enzyme into nanopores different nature on (2D-3D transition) also studied. results electrochemical reduction bactosomes functionally active microsomal monooxygenase system are considered. and electrocatalytic parameters were compared for generation metabolites.
Language: Английский
Citations
1
Microchemical Journal, Journal Year: 2024, Volume and Issue: unknown, P. 112377 - 112377
Published: Dec. 1, 2024
Language: Английский
Citations
1
BioNanoScience, Journal Year: 2024, Volume and Issue: 14(3), P. 2930 - 2939
Published: July 12, 2024
Language: Английский
Citations
0