Study of QSAR ,Molecular Modeling and Docking of Some N,N-dimethyl Carbamate Derivatives as Acetyl cholinesterase Inhibitor

Abstract

N,N- dimethyl carbamate has been commonly used as acetyl cholinesterase inhibitor , a series of N,N-di benzyl amino derivatives were subjected to two dimension (2D) quantitative structure activity relationship and (2D-QSAR)studies . The 2D-QSAR models were constructed on a for word of partial least sequence (PLS) and step wise multiple regression (SW-MLR) . By using MOE procedure and by choosing randomly descriptors as independent variable and plotted against biological activity as dependent variable a number of QSAR equations were obtained the best of them were: • PIC50= 5.89187-0.06775 LogP-0.01059 PEOE-VSA-1 R2 = 0.86 RMSE = 0.12 As a result from this equation forty compound was designed and made a dock in to the active site of selected receptor (1EVE) which was retrieved from protein data bank. The most active compounds 19 and 20 that have free energy interaction better than compound 5 as reference compound , and were find that the electron-withdrawal substituent's on aromatics rings of the dibenzylamino group reduce the inhibitory power.