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Novel organoruthenium(II) complex C1 selectively inhibits butyrylcholinesterase without side effects on neuromuscular transmission [Elektronski vir]Trobec, Tomaž ...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 [(n6-pcymene) Ru(II)(1-hydroxy-3-methoxypyridine-2(1H)-thionato)pta]PF6 (C1) 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 IC50 value of 2.88 μM. When tested at supra-pharmacological concentrations (30, 60, 90, and 120 μM), C1 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), C1 had no effect on resting membrane potential, but significantly decreased the amplitude of miniature endplate potentials (MEPP) without reducing their frequency. The same concentration of C1 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, C1 does not importantly affect the physiology of neuromuscular transmission and skeletal muscle contraction.Source: International journal of molecular sciences [Elektronski vir]. - ISSN 1422-0067 (Vol. 24, iss. 3, [article no.] 2681, 2023, str. 1-14)Type of material - e-article ; adult, seriousPublish date - 2023Language - englishCOBISS.SI-ID - 140487427
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Trobec, Tomaž | 51852 |
Žužek, Monika C. | 22588 |
Sepčić, Kristina | 15328 |
Kladnik, Jerneja | 39077 |
Turel, Iztok | 11053 |
Frangež, Robert | 12449 |
Source: Personal bibliographies
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