20.500.12556/RUL-144178 Novel organoruthenium(II) complex C1 selectively inhibits butyrylcholinesterase without side effects on neuromuscular transmission 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$^6$-p-cymene)Ru(II)(1-hydroxy-3-methoxypyridine-2(1H)-thionato)pta]PF$_6$ (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 IC$_{50}$ 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 end-plate 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. organoruthenium(II) complex acetylcholinesterase butyrylcholinesterase mouse neuromuscular system ruthenium Alzheimer disease neurodegenerative diseases true false true Angleški jezik Ni določen Članek v reviji 2023-02-02 14:29:03 2023-02-02 14:29:08 2024-02-27 11:16:02 0000-00-00 00:00:00 2023 0 0 14 str. iss. 3, art. 2681 Vol. 24 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-092 1422-0067 10.3390/ijms24032681 140487427 Novel-Zuzek.pdf Novel-Zuzek.pdf 1 5AB8FB69325934AB06CECDA1F8687471 19f8d9e9066ff8d0afcc5d6053ca4c1f3ef5f49ee023d38ba39ed4eb5b50cf94 439c6c42-a2fe-11ed-9c94-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=166368 https://www.mdpi.com/1422-0067/24/3/2681 1 48a42516-a2fd-11ed-9c94-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=166367 Veterinarska fakulteta Biotehniška fakulteta Fakulteta za kemijo in kemijsko tehnologijo 0 0 0