Spirocyclohexadienones as an Uncommon Scaffold for Acetylcholinesterase Inhibitory Activity.

The potential of inhibition of a set of some spirocyclohexadienones, readily synthesized in two steps and good overall yield from Morita-Baylis-Hillman adducts, was evaluated in vitro against acetylcholinesterase. We found that eight of them are able to inhibit the acetylcholinesterase activity, with IC50 values ranging from 0.12 to 12.67 μM. Molecular docking study indicated that the spirocyclohexadienone, 9e (IC50 = 0.12 μM), a mixed-type AChE inhibitor, showed a good interaction at active site of the enzyme, including the cationic (CAS) and the peripheral site (PAS). Thus, we have found bioactive compounds for further studies aimed at the discovery of more potent acetylcholinesterase inhibitors. As far as we know, this is the first report describing the anti-cholinesterase effect of this class of compounds.