QSAR analysis of the acetylcholinesterase inhibitory activity of some tertiary amine derivatives of cinnamic acid

Abstract

Acetylcholinesterase (AChE) is an essential enzyme in the nervous system that increases the rate of the hydrolysis of the neurotransmitter acetylcholine. Excessive hydrolysis of acetylcholine is one of the factors that cause Alzheimer’s disease, and the inhibition of AChE might be one way to prevent and control the disease. In the present study, a QSAR study was developed on a set of 72 tertiary amine derivatives of cinnamic acids as a new family of acetylcholinesterase inhibitors. Enhanced replacement method (ERM) was used for variable selection, and multiple linear regression (MLR) was performed to correlate between structural features of molecules and their acetylcholinesterase inhibitory activity. The result suggests that the four variables, namely, HVcpx, VEA2, HATS5u, and qpmax indices, play an important role in the AChE inhibitory activities. The proposed model exhibited good statistical parameters for the training set (with R2train = 0.913, q2LOO = 0.896, F-ratio = 140.04) and test set (R2test = 0.856, $$ {r}_m^2 $$ =0.79, $$ {r}_m^{\prime 2}=0.66 $$ , $$ \overline{r_m^2}=0.72 $$ , and $$ {\Delta r}_m^2=0.13 $$ ).