Comprehensive analysis of acetylcholinesterase inhibitor and reactivator complexes: implications for drug design and antidote development.

Autor: Bagrowska W; Tunneling Group, Biotechnology Centre, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland., Karasewicz A; Tunneling Group, Biotechnology Centre, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland., Góra A; Tunneling Group, Biotechnology Centre, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland. Electronic address: artur.gora@polsl.pl.
Jazyk: angličtina
Zdroj: Drug discovery today [Drug Discov Today] 2024 Dec; Vol. 29 (12), pp. 104217. Date of Electronic Publication: 2024 Oct 29.
DOI: 10.1016/j.drudis.2024.104217
Abstrakt: The main function of acetylcholinesterase (AChE) is to regulate the levels of one of the most important neurotransmitters: acetylcholine. This makes AChE an ideal molecular target for the treatment of neurodegenerative diseases and dementia (such as Alzheimer's disease), as well as for the neutralisation of natural toxins (e.g., venom peptides) and chemical warfare agents. The significance of AChE inhibitors in slowing the progression of dementia, as well as the role of reactivators in treating poisoned individuals, is reflected in several co-crystallised complexes deposited in the Protein Data Bank. In this study, we analysed all deposited AChE-small-molecule complexes to gain insights into compound binding and to provide guidance for the future design of therapeutic drugs and new antidotes.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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