Fine tuning of cholinesterase and glutathione-S-transferase activities by organoruthenium(II) complexes

Trobec, Tomaž (author), Sepčić, Kristina (author), Žužek, Monika C. (author), Kladnik, Jerneja (author), Podjed, Nina (author), Cardoso Páscoa, Catarina (author), Turel, Iztok (author), Frangež, Robert (author)

Cholinesterases (ChEs) show increased activities in patients with Alzheimer’s disease, and remain one of the main therapeutic targets for treatment of this neurodegenerative disorder. A library of organoruthenium(II) complexes was prepared to investigate the influence of their structural elements on inhibition of ChEs, and on another pharmacologically important group of enzymes, glutathione S-transferases (GSTs). Two groups of organoruthenium(II) compounds were considered: (i) organoruthenium(II) complexes with p-cymene as an arene ligand, and (ii) organoruthenium(II) carbonyl complexes as CO-releasing molecules. Eight organoruthenium complexes were screened for inhibitory activities against ChEs and GSTs of human and animal origins. Some compounds inhibited all of these enzymes at low micromolar concentrations, while others selectively inhibited either ChEs or GSTs. This study demonstrates the importance of the different structural elements of organoruthenium complexes for their inhibitory activities against ChEs and GSTs, and also proposes some interesting compounds for further preclinical testing as ChE or GST inhibitory drugs.

• Language: English
• Keywords: cholinesterase, enzyme inhibition, glutathione S-transferase, organoruthenium complex, pyrithione, β-diketone, carbonyl, glutathione transferase
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: VF - Veterinary Faculty; BF - Biotechnical Faculty; FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: 16 str.
• Numbering: Vol. 9, iss. 9, art. 1243
• PID: 20.500.12556/RUL-136344
• UDC: 636.09:612
• ISSN on article: 2227-9059
• DOI: 10.3390/biomedicines9091243
• COBISS.SI-ID: 76757507
• Publication date in RUL: 25.04.2022

Record is a part of a journal

• Title: Biomedicines
• Shortened title: Biomedicines
• Publisher: MDPI
• ISSN: 2227-9059
• COBISS.SI-ID: 523006745

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 16.09.2021