Anticancer activities of cyclohexenone derivatives

We designed 21 ethyl 3,5-diphenyl-2-cyclohexenone-6-carboxylate derivatives to identify compounds exhibiting anticancer activity. To measure the inhibitory effects of the compounds on cancer cell growth, a long-term survival clonogenic assay was performed. Since compounds containing a cyclohexenone moiety inhibit the enzyme acetylcholinesterase, an in vitro acetylcholinesterase assay was performed for all 21 cyclohexenone derivatives. To examine the effect of the derivative that exhibited the best cancer cell growth inhibition on the induction of apoptosis by demonstrating the activation of caspases and apoptosis regulatory proteins, immunoblotting and immunofluorescence microscopic analyses were performed. The binding mode between the cyclohexenone derivatives and acetylcholinesterase was elucidated at the molecular level using in silico docking. Druggability was evaluated based on ligand efficiency.