Novel Tacrine and Hesperetin analogues: Design, Molecular docking and in silico ADME studies to identify potential Acetyl choline esterase inhibitors for Alzheimer’s disease.

Abstract

Alzheimer’s disease is considered as most prevailing and common CNS disease found in elder population over 60 years of age. The early diagnosis of the disease prior to the occurrence of first behavioral symptom, dementia is difficult and hence the management of dementia and alleviation of other symptoms is the only available treatment for the AD. Acetyl cholinesterase inhibitors (AchE) are widely used in the treatment. In this study two series of new Tacrine(T1-T9) and Hesperetin derivatives(H1-H9) on the basis of the structural characteristics of acetyl cholinesterase (AchE) inhibitors were designed and screened to identify potential analogues as Anti-Alzheimer drug on the AchE (PDB ID:1DX4) using GLIDE employing extra-precision docking. The docking results Glide score, XPscore, docking score and binding interactions were compared with standard drug Tacrine. From the docking results it was found that T9 showed highest docking score among the designed compounds. The ADME properties also predicted using Qikprop application, from the above studies potential analogues with highest AchE inhibition and excellent pharmacokinetic properties were identified.