Submit Manuscript  

Article Details


Spirocyclohexadienones as an Uncommon Scaffold for Acetylcholinesterase Inhibitory Activity

Author(s):

Ralph C. Gomes, Renata P. Sakata*, Wanda P. Almeida* and Fernando Coelho*  

Abstract:


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.

Keywords:

Alzheimer disease, Morita-Baylis-Hillman, Spirocyclohexadienones, heterocycles, Acetylcholinesterase, Inhibitors

Affiliation:

Laboratório de Síntese de Produtos Naturais e Fármacos - Institute of Chemistry, University of Campinas, PO Box 6154 – 13083-970 – Campinas, SP , Laboratório de Síntese de Produtos Naturais e Fármacos - Institute of Chemistry, University of Campinas, PO Box 6154 – 13083-970 – Campinas, SP , Laboratório de Síntese de Produtos Naturais e Fármacos - Institute of Chemistry, University of Campinas, PO Box 6154 – 13083-970 – Campinas, SP , Laboratório de Síntese de Produtos Naturais e Fármacos - Institute of Chemistry, University of Campinas, PO Box 6154 – 13083-970 – Campinas, SP



Full Text Inquiry