Spectroscopic study, Quantum Chemical Investigations, In silico and Drug Likeness of 4-Chloro-6,7-dimethoxyquinazoline: A potent study of new anti-alzheimer agent

Abstract

Alzheimer's disease (AD) is one of the most severe illnesses linked to aging. The present work examined the potential of 4-Chloro-6,7-dimethoxyquinazoline (CDQ) as anti-alzheimer drug using spectroscopic (FT-IR, FT-Raman, and UV-Vis)and computational techniques. The molecular geometries of CDQ were optimized using DFT/B3LYP/6-311++G(d,p). Thecalculation of vibrational frequencies is based on the potential energy distribution (PED). The calculated frequencies usingDFT matches well with the experimental values. Time-dependent density functional theory (TD-DFT) have been used tostudy the frontier molecular orbitals (FMO) in order to determine the energy gap, global reactive parameters, and otherrelated molecular features. The molecular electrostatic potential (MEP) and the mulliken charge analysis determine theregions that are most susceptible to electrophilic and nucleophilic attacks. The charge delocalization and stability of thestudied molecule were examined using Natural Bond Orbital (NBO) analysis. Multiwfn software had been employed toperform the topological studies of LOL, RDG, NCI, and ELF. In order to validate the biological activity, molecular dockingstudies were carried out to stimulate the binding orientation and affinity of CDQ against four AChE proteins. According toour docking analysis, CDQ and the 4EY7 protein have a significant interaction, with a binding energy of -7.5 kcal mol-1.In addition, the stability of the protein-ligand interaction had been assessed using molecular dynamics simulations. Studieson the ADMET prediction of CDQ have also been carried out. These findings provide a very interesting and feasible detailsregarding the title compound for potential future investigation.