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Inhibitory properties of quinopimaric acid derivatives towards cholinesterases
Elena Tretyakova1, Niels V Heise2, René Csuk2
1Ufa Institute of Chemistry of the Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Russian Federation.
Abstract:
A series of new diterpene quinopimaric acid derivatives modified at the hydroxyl group with different pharmacophore fragments has been synthesised and their (along with previously obtained compounds) inhibitory properties towards cholinesterases were studied. Thereby an indole-3-acetyl derivative 7 and a propargyl substituted compound 28 were shown to be excellent and acetylcholinesterase-selective inhibitors. Both compounds inhibited the enzyme as a mixed type inhibitor, and Ki values of 0.41 and 0.44 µM and Ki' values of 0.98 and 2.26 µM were determined. The binding interactions between all active compounds and ligands protein were confirmed through molecular docking study.
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