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Advances in cholinesterase inhibitor research : an overview of preclinical studies of selected organoruthenium(II) complexes
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Žužek, Monika C.
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https://www.mdpi.com/1422-0067/25/16/9049
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Abstract
Cholinesterase (ChE) inhibitors are crucial therapeutic agents for the symptomatic treatment of certain chronic neurodegenerative diseases linked to functional disorders of the cholinergic system. Significant research efforts have been made to develop novel derivatives of classical ChE inhibitors and ChE inhibitors with novel scaffolds. Over the past decade, ruthenium complexes have emerged as promising novel therapeutic alternatives for the treatment of neurodegenerative diseases. Our research group has investigated a number of newly synthesized organoruthenium(II) complexes for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Three complexes (C1a, C1-C, and C1) inhibit ChE in a pharmacologically relevant range. C1a reversibly inhibits AChE and BChE without undesirable peripheral effects, making it a promising candidate for the treatment of Alzheimer’s disease. C1-Cl complex reversibly and competitively inhibits ChEs, particularly AChE. It inhibits nerve-evoked skeletal muscle twitch and tetanic contraction in a concentration-dependent manner with no effect on directly elicited twitch and tetanic contraction and is promising for further preclinical studies as a competitive neuromuscular blocking agent. C1 is a selective, competitive, and reversible inhibitor of BChE that inhibits horse serum BChE (hsBChE) without significant effect on the peripheral neuromuscular system and is a highly species-specific inhibitor of hsBChE that could serve as a species-specific drug target. This research contributes to the expanding knowledge of ChE inhibitors based on ruthenium complexes and highlights their potential as promising therapeutic candidates for chronic neurodegenerative diseases.
Language:
English
Keywords:
cholinesterases
,
enzyme inhibition
,
organoruthenium complex
,
neuromuscular junction
,
mouse
,
enzymes
Work type:
Article
Typology:
1.02 - Review Article
Organization:
VF - Veterinary Faculty
Publication status:
Published
Publication version:
Version of Record
Year:
2024
Number of pages:
14 str.
Numbering:
Vol. 25, iss. 16, art. 9049
PID:
20.500.12556/RUL-160379
UDC:
616-092
ISSN on article:
1422-0067
DOI:
10.3390/ijms25169049
COBISS.SI-ID:
205157635
Publication date in RUL:
27.08.2024
Views:
87
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18
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Record is a part of a journal
Title:
International journal of molecular sciences
Shortened title:
Int. j. mol. sci.
Publisher:
MDPI
ISSN:
1422-0067
COBISS.SI-ID:
2779162
Licences
License:
CC BY 4.0, Creative Commons Attribution 4.0 International
Link:
http://creativecommons.org/licenses/by/4.0/
Description:
This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Licensing start date:
27.08.2024
Projects
Funder:
ARIS - Slovenian Research and Innovation Agency
Project number:
P4-0053
Name:
Endokrini, imunski in encimski odzivi pri zdravih in bolnih živalih
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