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Structural isomerism and enhanced lipophilicity of pyrithione ligands of organoruthenium(II) complexes increase inhibition on AChE and BuChE
ID Kladnik, Jerneja (Avtor), ID Ristovski, Samuel (Avtor), ID Kljun, Jakob (Avtor), ID Defant, Andrea (Avtor), ID Mancini, Ines (Avtor), ID Sepčić, Kristina (Avtor), ID Turel, Iztok (Avtor)

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Izvleček
The increasing number of Alzheimer’s disease (AD) cases requires the development of new improved drug candidates, possessing the ability of more efficient treatment as well as less unwanted side effects. Cholinesterase enzymes are highly associated with the development of AD and thus represent important druggable targets. Therefore, we have synthesized eight organoruthenium(II) chlorido complexes 1a–h with pyrithione-type ligands (pyrithione = 1-hydroxypyridine-2(1H)-thione, a), bearing either pyrithione a, its methyl (b-e) or bicyclic aromatic analogues (f–h) and tested them for their inhibition towards electric eel acetylcholinesterase (eeAChE) and horse serum butyrylcholinesterase (hsBuChE). The experimental results have shown that the novel complex 1g with the ligand 1-hydroxyquinoline-2-(1H)-thione (g) improves the inhibition towards eeAChE (IC$_{50}$ = 4.9 µM) and even more potently towards hsBuChE (IC$_{50}$ = 0.2 µM) in comparison with the referenced 1a. Moreover, computational studies on Torpedo californica AChE have supported the experimental outcomes for 1g, possessing the lowest energy value among all tested complexes and have also predicted several interactions of 1g with the target protein. Consequently, we have shown that the aromatic ring extension of the ligand a, though only at the appropriate position, is a viable strategy to enhance the activity against cholinesterases.

Jezik:Angleški jezik
Ključne besede:Alzheimer’s disease, acetylcholinesterase, butyrylcholinesterase, cholinesterase inhibitor, molecular docking, organoruthenium(II) complexes, pyrithione derivatives
Vrsta gradiva:Članek v reviji
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:FKKT - Fakulteta za kemijo in kemijsko tehnologijo
BF - Biotehniška fakulteta
Status publikacije:Objavljeno
Različica publikacije:Objavljena publikacija
Leto izida:2020
Št. strani:17 str.
Številčenje:Vol. 21, iss. 16, art. 5628
PID:20.500.12556/RUL-134383 Povezava se odpre v novem oknu
UDK:546.96
ISSN pri članku:1661-6596
DOI:10.3390/ijms21165628 Povezava se odpre v novem oknu
COBISS.SI-ID:24569091 Povezava se odpre v novem oknu
Datum objave v RUL:12.01.2022
Število ogledov:889
Število prenosov:137
Metapodatki:XML RDF-CHPDL DC-XML DC-RDF
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Gradivo je del revije

Naslov:International journal of molecular sciences
Skrajšan naslov:Int. j. mol. sci.
Založnik:MDPI
ISSN:1661-6596
COBISS.SI-ID:36217605 Povezava se odpre v novem oknu

Licence

Licenca:CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
Začetek licenciranja:06.08.2020

Sekundarni jezik

Jezik:Slovenski jezik
Ključne besede:rutenij, organorutenijevi kompleksi, ligandi, derivati piritiona, Alzheimerjeva bolezen

Projekti

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

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

Financer:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Program financ.:Young researchers

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