Cholesterol Oxime Olesoxime Assessed as a Potential Ligand of Human Cholinesterases DOI Creative Commons
Dora Kolić, Goran Šinko, Ludovic Jean

и другие.

Biomolecules, Год журнала: 2024, Номер 14(5), С. 588 - 588

Опубликована: Май 15, 2024

Olesoxime, a cholesterol derivative with an oxime group, possesses the ability to cross blood–brain barrier, and has demonstrated excellent safety tolerability properties in clinical research. These characteristics indicate it may serve as centrally active ligand of acetylcholinesterase (AChE) butyrylcholinesterase (BChE), whose disruption activity organophosphate compounds (OP) leads uncontrolled excitation potentially life-threatening symptoms. To evaluate olesoxime binding reactivator human AChE BChE, we conducted vitro kinetic studies metabolite insecticide parathion, paraoxon, warfare nerve agents sarin, cyclosarin, tabun, VX. Our results showed that both enzymes possessed affinity for mid-micromolar range, higher than antidotes use (i.e., 2-PAM, HI-6, etc.). While weak reactivate AChE, cyclosarin-inhibited BChE was reactivated overall reactivation rate constant comparable standard HI-6. Moreover, combination maximum increased by 10–30% cyclosarin- sarin-inhibited BChE. Molecular modeling revealed productive interactions between highlighting BChE-targeted therapy. might be added OP poisoning treatment increase efficacy reactivation, its scaffold could provide basis development novel antidotes.

Язык: Английский

25-Hydroxycholesterol modulates synaptic vesicle endocytosis at the mouse neuromuscular junction DOI
Eva A. Kuznetsova,

Guzalia F. Zakirjanova,

Andrei N. Tsentsevitsky

и другие.

Pflügers Archiv - European Journal of Physiology, Год журнала: 2025, Номер 477(3), С. 421 - 439

Опубликована: Янв. 9, 2025

Язык: Английский

Процитировано

2

25-Hydroxycholesterol as a negative regulator of diaphragm muscle contractions via estrogen receptor and Ca2+ -dependent pathway DOI
Eva A. Kuznetsova, Nikita S. Fedorov,

Guzel F. Zakyrjanova

и другие.

Histochemistry and Cell Biology, Год журнала: 2025, Номер 163(1)

Опубликована: Апрель 3, 2025

Язык: Английский

Процитировано

0

Effects of 24-Hydroxycholesterol on the ATP-Induced Trigeminal Nerve Electrical Activity and the Mast Cells Degranulation DOI

K. R. Gilizhdinova,

Dinara Nurmieva, Anton Ananev

и другие.

Biochemistry (Moscow) Supplement Series A Membrane and Cell Biology, Год журнала: 2025, Номер 19(1), С. 52 - 59

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0

25-hydroxycholesterol triggers antioxidant signaling in mouse atria DOI

Julia G. Odnoshivkina,

Alexey M. Petrov

Prostaglandins & Other Lipid Mediators, Год журнала: 2024, Номер 172, С. 106834 - 106834

Опубликована: Март 22, 2024

Язык: Английский

Процитировано

1

Cholesterol Oxime Olesoxime Assessed as a Potential Ligand of Human Cholinesterases DOI Creative Commons
Dora Kolić, Goran Šinko, Ludovic Jean

и другие.

Biomolecules, Год журнала: 2024, Номер 14(5), С. 588 - 588

Опубликована: Май 15, 2024

Olesoxime, a cholesterol derivative with an oxime group, possesses the ability to cross blood–brain barrier, and has demonstrated excellent safety tolerability properties in clinical research. These characteristics indicate it may serve as centrally active ligand of acetylcholinesterase (AChE) butyrylcholinesterase (BChE), whose disruption activity organophosphate compounds (OP) leads uncontrolled excitation potentially life-threatening symptoms. To evaluate olesoxime binding reactivator human AChE BChE, we conducted vitro kinetic studies metabolite insecticide parathion, paraoxon, warfare nerve agents sarin, cyclosarin, tabun, VX. Our results showed that both enzymes possessed affinity for mid-micromolar range, higher than antidotes use (i.e., 2-PAM, HI-6, etc.). While weak reactivate AChE, cyclosarin-inhibited BChE was reactivated overall reactivation rate constant comparable standard HI-6. Moreover, combination maximum increased by 10–30% cyclosarin- sarin-inhibited BChE. Molecular modeling revealed productive interactions between highlighting BChE-targeted therapy. might be added OP poisoning treatment increase efficacy reactivation, its scaffold could provide basis development novel antidotes.

Язык: Английский

Процитировано

1