ABSTRACT
Cinnamic anhydrides have been shown to be more than reactive reagents, but they also act as inhibitors of the enzyme acetylcholinesterease (AChE). Thus, out of a set of 33 synthesised derivatives, several of them were mixed type inhibitors for AChE (from electric eel). Thus, (E)-3-(2,4-dimethoxyphenyl)acrylic anhydride (2c) showed Kiâ¯=â¯8.30⯱â¯0.94⯵M and Ki'â¯=â¯9.54⯱â¯0.38⯵M, and for (E)-3-(3-chlorophenyl)acrylic anhydride (2u) Kiâ¯=â¯8.23⯱â¯0.93⯵M and Ki'â¯=â¯13.07⯱â¯0.46⯵M were measured. While being not cytotoxic to many human cell lines, these compounds showed an unprecedented and noteworthy inhibitory effect for AChE but not for butyrylcholinesterase (BChE).
Subject(s)
Acetylcholinesterase/chemistry , Butyrylcholinesterase/chemistry , Cholinesterase Inhibitors/pharmacology , Cinnamates/chemistry , Ethylene Oxide/pharmacology , Cell Proliferation , Cholinesterase Inhibitors/chemistry , Ethylene Oxide/analogs & derivatives , Ethylene Oxide/chemistry , Humans , Molecular Docking Simulation , Molecular Structure , Neoplasms/drug therapy , Neoplasms/pathology , Protein Conformation , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
Unexpected inhibitory effects against eeAChE could be found for a newly synthesized class of caffeic acid phenethyl ester (CAPE) derivatives. Thus, phenethyl-(E)-3-(3,5-dimethoxy-4-phenethoxyphenyl)-acrylate (Kiâ¯=â¯1.97⯱â¯0.38⯵M, Ki´â¯=â¯2.44⯱â¯0.07⯵M) and 4-(2-(((E)-3-(3,4-bis(benzyloxy)phenyl)acryloyl)oxy)ethyl)-1,2-phenylene (2E,2'E)-bis(3-(3,4-bis(benzyloxy)phenyl)acrylate) (Kiâ¯=â¯0.72⯱â¯0.31⯵M, Ki´â¯=â¯1.80⯱â¯0.21⯵M) showed very good inhibition of eeAChE, while being non cytotoxic for malignant human cancer cells and non-malignant mouse fibroblasts. Also, they are weak inhibitors for BChE (from equine serum).
