Abstract
Six known products ( 4 – 9 ) were prepared from reaction of adipoyl chloride with 1,2,3-trimethoxybenzene according to the literature. From (2,3,4-trimethoxyphenyl)(2-(2,3,4-trimethoxyphenyl)cyclopent-1-en-1-yl)methanone ( 4 ) of them, four new 1,2-disubstituted cyclopentane derivatives ( 10–13 ) with phenyl and benzyl units were synthesized by reactions such as hydrazonation, catalytic hydrogenation and bromination. The obtained compounds 4–13 were examined for their in vitro inhibitory activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and α-glucosidase enzymes. All compounds 4–13 showed inhibition at nanomolar level with K i values in the range of 45.53 ± 7.35–631.96 ± 18.88 nM for AChE, 84.30 ± 9.92–622.10 ± 35.14 nM for BChE, and 25.47 ± 4.46–48.87 ± 7.33 for α-Glu. In silico molecular docking studies of the potent compounds were performed in the active sites of AChE (PDB: 1E66), BChE (PDB: 1P0I), and α-glucosidase (PDB: 5ZCC) to compare the effect of bromine atom on the inhibition mechanism. The optimized molecular structures, HOMO–LUMO energies and molecular electrostatic potential maps for the compounds were calculated by using density functional theory with B3LYP/6–31 + G(d,p).