2D-QSAR Studies of Tacrine Analogues for Acetylcholine Esterase (AChE) Inhibition using Multiple Linear Regression Analysis

Abstract

Quantitative structure–activity relationship (QSAR) of tacrine analogues for acetylcholine esterase (AChE) inhibitory activity was studied using stepwise multiple linear regression (MLR). AChE activity (pIC50) of tacrine derivatives was expressed with acceptable explanation (95.5%) in Model (1) and other statistically acceptable predictive power (76.7-93.6 %) (Models 2-6). Though Model (5) was the best equation with better prediction and with a smaller standard error than other methods, it did not give a good correlation with the external training set. Model (3) showed higher correlation coefficient (61.03%) than the others. The resulting models with the given descriptors illustrate the significant role of T_N_Cl_4 & 6, T_C_O_7 and T_2_O_7 on increasing AChE activity and all other descriptors in the equations amounted to decrease in AChE activity. The QSAR studies provide useful information for design of new ligands. Keywords: 2D QSAR; Acetylcholine Esterase; Alignment independent descriptors; Alzheimers; Stepwise multiple linear regression; Tacrine