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Home / Equine Research Bank / Int J Mol Sci / Novel Organoruthenium(II) Complex C1 Selectively Inhibits Bu...
International journal of molecular sciences2023; 24(3); 2681; doi: 10.3390/ijms24032681

Novel Organoruthenium(II) Complex C1 Selectively Inhibits Butyrylcholinesterase without Side Effects on Neuromuscular Transmission.

Abstract: Enzyme butyrylcholinesterase (BChE) shows increased activity in some brain regions after progression of Alzheimer's disease and is therefore one of the therapeutic targets for symptomatic treatment of this neurodegenerative disorder. The organoruthenium(II) complex [(η--cymene)Ru(II)(1-hydroxy-3-methoxypyridine-2(1)-thionato)pta]PF () was designed based on the results of our previous structure-activity studies. Inhibitory activity toward cholinesterase enzymes shows that this complex selectively, competitively, and reversibly inhibits horse serum BChE (hsBChE) with an IC value of 2.88 µM. When tested at supra-pharmacological concentrations (30, 60, 90, and 120 µM), had no significant effect on the maximal amplitude of nerve-evoked and directly elicited single-twitch and tetanic contractions. At the highest tested concentration (120 µM), had no effect on resting membrane potential, but significantly decreased the amplitude of miniature end-plate potentials (MEPP) without reducing their frequency. The same concentration of had no effect on the amplitude of end-plate potentials (EPP), however it shortened the half-decay time of MEPPs and EPPs. The decrease in the amplitude of MEPPs and shortening of the half-decay time of MEPPs and EPPs suggest a possible weak inhibitory effect on muscle-type nicotinic acetylcholine receptors (nAChR). These combined results show that, when applied at supra-pharmacological concentrations up to 120 µM, does not importantly affect the physiology of neuromuscular transmission and skeletal muscle contraction.
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Publication Date: 2023-01-31 PubMed ID: 36769002PubMed Central: PMC9916964DOI: 10.3390/ijms24032681Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article discusses a compound called Organoruthenium(II) Complex C1 that has been found to selectively inhibit the enzyme butyrylcholinesterase (BChE), linked with Alzheimer’s disease, without interfering with neuromuscular transmission or muscular contractions.

Research Context and Hypothesis

  • The researchers intended to investigate the inhibitory effect of Organoruthenium(II) Complex C1, a compound specifically designed based on previous structure-activity studies, on the enzyme Butyrylcholinesterase (BChE).
  • BChE plays a significant role in the progression of Alzheimer’s disease; thus, it is a key target for possible therapeutic treatments.
  • The researchers hypothesized that the Organoruthenium(II) Complex C1 would selectively inhibit BChE without affecting neuromuscular transmission or muscle contractions.

Research Methodologies and Findings

  • They tested the Organoruthenium(II) Complex C1 on horse serum BChE (hsBChE) and measured its inhibitory activity. They found the compound was effective, working both selectively and in a reversible manner, and provided an IC value of 2.88 µM, which indicates the effectiveness of the inhibitor.
  • They then tested the compound at higher concentrations (30, 60, 90, and 120 µM) to analyze its effects on neuromuscular contractions. They found no significant change in the amplitude of nerve-evoked and directly elicited single-twitch and tetanic contractions.
  • At the highest tested concentration (120 µM), the compound showed no effect on resting membrane potential but did decrease the amplitude of miniature end-plate potentials (MEPPs) without affecting their frequency.
  • In higher concentrations, the compound also showed no effect on the amplitude of end-plate potentials (EPPs), but did shorten the half-decay time of both MEPPs and EPPs – suggesting a minor inhibitory effect on muscle-type nicotinic acetylcholine receptors (nAChR).

Conclusion of the Research

  • The data gathered showed that even in supra-pharmacological concentrations (up to 120 µM), the Organoruthenium(II) Complex C1 did not significantly impact neuromuscular transmission or skeletal muscle contraction.
  • The research thus indicated that this compound successfully suppresses BChE – an enzyme implicated in Alzheimer’s disease – without significant side effects on basic muscle functioning and neuromuscular transmission.
  • This breakthrough indicates the significant potential of Organoruthenium(II) Complex C1 in the therapeutic treatment of Alzheimer’s disease.

Cite This Article

APA
Trobec T, Žužek MC, Sepčić K, Kladnik J, Turel I, Frangež R. (2023). Novel Organoruthenium(II) Complex C1 Selectively Inhibits Butyrylcholinesterase without Side Effects on Neuromuscular Transmission. Int J Mol Sci, 24(3), 2681. https://doi.org/10.3390/ijms24032681

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 24
Issue: 3
PII: 2681

Researcher Affiliations

Trobec, Tomaž
  • Institute of Preclinical Sciences, Veterinary Faculty, University of Ljubljana, Gerbičeva 60, 1000 Ljubljana, Slovenia.
Žužek, Monika C
  • Institute of Preclinical Sciences, Veterinary Faculty, University of Ljubljana, Gerbičeva 60, 1000 Ljubljana, Slovenia.
Sepčić, Kristina
  • Department of Biology, Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101, 1000 Ljubljana, Slovenia.
Kladnik, Jerneja
  • Department of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia.
Turel, Iztok
  • Department of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia.
Frangež, Robert
  • Institute of Preclinical Sciences, Veterinary Faculty, University of Ljubljana, Gerbičeva 60, 1000 Ljubljana, Slovenia.

MeSH Terms

  • Animals
  • Horses
  • Neuromuscular Junction / physiology
  • Butyrylcholinesterase
  • Synaptic Transmission / physiology
  • Membrane Potentials
  • Muscle Contraction

Grant Funding

  • P4-0053 / Slovenian Research Agency
  • P1-0207 / Slovenian Research Agency
  • P1-0175 / Slovenian Research Agency

Conflict of Interest Statement

The authors declare no conflict of interest.

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