Discovery of antitumor activity of cisplatin and its analogues, as well as their successful medical application in the treatment of a plethora of tumours and symptomatic treatment of Alzheimer disease (AD), revived interest in research and development of new platinum- and other metal-based drugs, e.g. ruthenium. Inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) has beneficial impact on AD patients. The result is increased concentration of acetylcholine in the synaptic cleft, which leads to improvement of cognitive functions. Glutathione S-transferase (GST) has increased expression in cancer cells; thus, GST inhibitors represent potential antitumor agents. In previous studies, ruthenium complexes have shown good anti-AChE, anti-BChE and anti-GST activity and as such possible therapeutic applications in the treatment of AD and cancer, where they act as multi-target drugs. Hence, we have tested 34 newly synthesized ruthenium complexes, their precursors and ligands on enzymes from animal and human origin. Results of this study have shown, that our newly synthesised ruthenium complexes have low or moderate inhibitory activity on the cholinesterases, whilst they lack GST inhibition. Anti-AChE activity is shown in 3 complexes and anti-BChE activity in 12 complexes when enzymes of animal origin are used. Anti-AChE activity of the enzyme of human origin was tested on 3 and shown in 2 compounds. Our study has opened new insight for further testing of ruthenium complexes as potential multi-target drugs and for novel therapy to treat tumours and neurodegenerative diseases.
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