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Structural and functional characterization of an organometallic ruthenium complex as a potential myorelaxant drug
Trobec, Tomaž (Avtor), Žužek, Monika C. (Avtor), Sepčić, Kristina (Avtor), Kladnik, Jerneja (Avtor), Kljun, Jakob (Avtor), Turel, Iztok (Avtor), Benoit, Evelyne (Avtor), Frangež, Robert (Avtor)

URLURL - Izvorni URL, za dostop obiščite https://www.sciencedirect.com/science/article/pii/S075333222030353X?via%3Dihub Povezava se odpre v novem oknu

Izvleček
In addition to antibacterial and antitumor effects, synthetic ruthenium complexes have been reported to inhibitseveral medicinally important enzymes, including acetylcholinesterase (AChE). They may also interact withmuscle-type nicotinic acetylcholine receptors (nAChRs) and thus affect the neuromuscular transmission andmuscle function. In the present study, the effects of the organometallic ruthenium complex of 5-nitro-1,10-phenanthroline (nitrophen) were evaluated on these systems. The organoruthenium-nitrophen complex [(η6-p-cymene)Ru(nitrophen)Cl]Cl; C22H21Cl2N3O2Ru (C1-Cl) was synthesized, structurally characterized and eval-uatedin vitrofor its inhibitory activity against electric eel acetylcholinesterase (eeAChE), human recombinantacetylcholinesterase (hrAChE), horse serum butyrylcholinesterase (hsBChE) and horse liver glutathione-S-transferase. The physiological effects of C1-Cl were then studied on isolated mouse phrenic nerve-hemi-diaphragm muscle preparations, by means of single twitch measurements and electrophysiological recordings.The compound C1-Cl acted as a competitive inhibitor of eeAChE, hrAChE and hsBChE with concentrationsproducing 50 % inhibition (IC50) of enzyme activity ranging from 16 to 26μM. Moreover, C1-Cl inhibited thenerve-evoked isometric muscle contraction (IC50= 19.44μM), without affecting the directly-evoked musclesingle twitch up to 40μM. The blocking effect of C1-Cl was rapid and almost completely reversed by neos-tigmine, a reversible cholinesterase inhibitor. The endplate potentials were also inhibited by C1-Cl in a con-centration-dependent manner (IC50= 7.6μM) without any significant change in the resting membrane potentialof musclefibers up to 40μM. Finally, C1-Cl (5–40μM) decreased (i) the amplitude of miniature endplatepotentials until a complete block by concentrations higher than 25μM and (ii) their frequency at 10μM or higherconcentrations. The compound C1-Cl reversibly blocked the neuromuscular transmissionin vitroby a non-de-polarizing mechanism and mainly through an action on postsynaptic nAChRs. The compound C1-Cl may betherefore interesting for further preclinical testing as a new competitive neuromuscular blocking, and thusmyorelaxant, drug

Jezik:Angleški jezik
Ključne besede:Organoruthenium nitrophenanthroline complex, acetylcholinesterase, butyrylcholinesterase, glutathione S-transferase, mouse neuromuscular system
Vrsta gradiva:Članek v reviji (dk_c)
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:VF - Veterinarska fakulteta
Leto izida:2020
Št. strani:Str. 1-11
Številčenje:Vol. 127, art. no. 110161
UDK:577.15:612.741
ISSN pri članku:1950-6007
DOI:10.1016/j.biopha.2020.110161 Povezava se odpre v novem oknu
COBISS.SI-ID:13704451 Povezava se odpre v novem oknu
Število ogledov:275
Število prenosov:50
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Gradivo je del revije

Naslov:Biomedicine & pharmacotherapy
Založnik:Elsevier
ISSN:1950-6007
COBISS.SI-ID:23136261 Povezava se odpre v novem oknu

Gradivo je financirano iz projekta

Financer:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Številka projekta:P4-0053
Naslov:Endokrini, imunski in encimski odzivi pri zdravih in bolnih živalih

Financer:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Številka projekta:P1-0207
Naslov:Toksini in biomembrane

Financer:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Številka projekta:P1-0175
Naslov:Napredna anorganska kemija

Licence

Licenca:CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
Povezava:http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
Opis:Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.
Začetek licenciranja:14.08.2020

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