Inhibitory properties of quinopimaric acid derivatives towards cholinesterases.

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 K i values of 0.41 and 0.44 µM and K i ' 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.