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). The calculation of vibrational frequencies is based on the potential energy distribution (PED). The calculated frequencies using DFT matches well with the experimental values. Time-dependent density functional theory (TD-DFT) have been used to study the frontier molecular orbitals (FMO) in order to determine the energy gap, global reactive parameters, and other related molecular features. The molecular electrostatic potential (MEP) and the mulliken charge analysis determine the regions that are most susceptible to electrophilic and nucleophilic attacks. The charge delocalization and stability of the studied molecule were examined using Natural Bond Orbital (NBO) analysis. Multiwfn software had been employed to perform the topological studies of LOL, RDG, NCI, and ELF. In order to validate the biological activity, molecular docking studies were carried out to stimulate the binding orientation and affinity of CDQ against four AChE proteins. According to our 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. Studies on the ADMET prediction of CDQ have also been carried out. These findings provide a very interesting and feasible details regarding the title compound for potential future investigation.