2D QSAR, design, docking study and ADMET of some N-aryl derivatives concerning inhibitory activity against Alzheimer disease

Abstract

Alzheimer disease (AD) is an ailment that disturbs mainly people of old age. The fundamental remedial way to deal with AD depends on the utilization of AChEI. The design of new intense and particular AChEI is critical in drug discovery. In silico technique will be used to solve the above problem. A new method was established to discover novel agents with better biological activity against Alzheimer disease. A validated model was established in this research to predict the biological activities of some anti-Alzheimer compounds and to design new hypothetical drugs influenced with molecular properties in the derived model; ATS4i, MATS2e, SpMax7_BhS, Energy(HOMO) and Molecular Weight and showed good correlation R2 = 0.936, R2adj = 0.907, Q2cv = 0.88, LOF = 0.0154 and R2ext = 0.881. All the descriptors in the model were in good agreement with the 15 test set predicted values. Five compounds were designed using D35rm as a template with improved activity. The compounds have higher and better binding scores (− 10.1, − 9.4, − 9.3, − 9.1 and − 8.1 all in kcal/mol) than the approved drugs (Donepezil =  − 7.4 kcal/mol). As the outcome, every one of the selected and the designed compounds is created and improved as potential anti-Alzheimer agents. Despite this, the further test examines and in vivo investigations are recommended to assess the method of the activities and other pharmacological impacts on these compounds.