Anticancer activities of cyclohexenone derivatives

Abstract

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.

Vimentin single cysteine residue acts as a tunable sensor for network organization and as a key for actin remodeling in response to oxidants and electrophiles

“…1 A). Thus, 2-cyclopentenone mimics the core reactive structure of the endogenous lipid mediators known as cyclopentenone prostaglandins [ 44 ]; 2-cyclohexenone is the reactive moiety of several anticancer compounds [ 45 ]; l -kynurenine is a product of tryptophan degradation by indoleamine 2,3-dioxygenase [ 46 ], and it is used here at the concentrations reached in experimental in vivo studies [ 47 ]; cysteamine is an endogenous aminothiol employed for the treatment of cystinosis [ 48 ]; 1,4-dinitro-1H-imidazole (DNI), and its mono-nitrated counterpart, 4-nitroimidazole (NI), bear analogy with nitroimidazole compounds used as antiparasitic agents, and previously reported to form adducts with parasite proteins [ 49 ]. The effects of these compounds on GFP-vimentin wt organization are illustrated in Fig.…”

Vimentin cysteine 328 modifications finely tune network organization and influence actin remodeling under oxidative and electrophilic stress

“…Thus, 2-cyclopentenone mimics the core reactive structure of the endogenous lipid mediators known as cyclopentenone prostaglandins [40]; 2-cyclohexenone is the reactive moiety of several anticancer compounds [41]; L-kynurenine is a product of tryptophan degradation by indoleamine 2,3-dioxygenase [42], and it is used here at the concentrations reached in experimental in vivo studies [43]; cysteamine is an endogenous aminothiol employed for the treatment of cystinosis [44]; 1,4-dinitro-1H-imidazole (DNI), and its mono-nitrated counterpart, 4nitroimidazole (NI), bear analogy with nitroimidazole compounds used as antiparasitic agents, and previously reported to form adducts with parasite proteins [45]. The effects of these compounds on GFP-vimentin wt organization are illustrated in Fig.…”