Structure-Based Drug Design of Novel Piperazine Containing Hydrazone Derivatives as Potent Alzheimer Inhibitors: Molecular Docking and Drug Kinetics Evaluation

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder that causes dementia and cognitive impairment in the elderly. The exact mechanism of the disease is still unknown. There are four medications available, all of which have a slew of negative side effects and only serve to improve patients' warning symptoms. Medicinal chemists are looking for treatments for this illness. The development and application of a novel class of multifunctional small molecule inhibitors is discussed. A variety of compounds were synthesized using the hydrazone scaffold. This is due to the ability of hydrazone derivatives to interfere with Amyloid beta (A) self-assembly, which is one of the causative agents in fibrils and oligomers. they can also counteract the impacts of toxic substances free radicals on useful therapeutic agents such as central nervous system penetrant drugs. In this study, structure-based drug design techniques utilized. Based on established literature studies and reasons such as lower resolution value (2.35), no mutation, Homo Sapiens, and X-ray diffraction method, a protein target (code ID 4EY7) was chosen. The protein target was designed to interact with compounds of interest (a lead compound with a higher binding energy), and was used as a template to design fifteen Hydrazone derivatives with greater interactions, higher binding scores, and improved enhanced drug-like properties and drug kinetic parameters The findings of these studies can be used to create promising pharmacotherapeutic compounds for the treatment of AD.