Correlation between structural propeties and bilogical activity of acetylcholinesterase in the presence of indanone and benzophenone derivatives inhibitors

One possible approach to treat Alzheimer’s disease (AD) is to restore acetylcholine levels by inhibiting acetylcholinesterase (AChE) with reversible inhibitors [1]. Clinical trials have shown that AChE inhibitors such as physostigmine, donepezil, rivastigime, and galantamine effectively improve memory in some patients. Beside the synthesis of the AChE inhibitors, QSAR studies were done on the variety of inhibitors. These techniques are very powerful tools for prediction of enzyme activity. It is also applicable in all area of science such as chemistry and physics. So we used QSAR methods for prediction of logIC50. In this work, QSAR of some indanone hybrids [2] and benzophenone [3] derivatives was studied using with large number of descriptors. The structure of inhibitors was drown and optimized in Hyperchem. Then, some of descriptors calculated by Hyperchem, Gaussian and Dragon softwares. The multiple linear regression was performed by SPSS. Different equations were obtained between log IC50 and descriptors. The free energy of interaction (docking energy) was estimated by Autodock.The following equation shows the correlation between logIC50 and of best selected descriptors. It has relatively good correlation. The descriptors were classified by PCA. Correlation between logIC50 and principal components is as follow: LogIC50=47.8140.007*(Mass)1.669(GGI4)+2.27(PJI3)+12.928(BEHm2)+0.043(RDF100u)+4.937(H ATS5)