Computational Investigation of 2,3-Dihydroquinazolin-4(1H)-one Derivatives as Multitarget Anti-Alzheimer Agents

DFT and Molecular Docking Studies against AChE, BChE, and BACE1

Authors

  • Abosede Adejoke Badeji
    Department of Chemical Sciences, Tai Solarin Federal University of Education, Ijagun, Ogun State, Nigeria
  • Olalekan Samuel
    Department of Physiology, Olabisi Onabanjo University, Sagamu Campus, Sagamu, Ogun State, Nigeria
  • Segun D. Oladipo
    Department of Chemical Sciences, Olabisi Onabanjo University, PMB 2002, Ago-Iwoye, Nigeria
  • Adejoke D. Osinubi
    Department of Chemical Sciences, Tai Solarin Federal University of Education, Ijagun, Ogun State, Nigeria
  • Adetoro A. Osanyinbi
    Department of Chemical Sciences, Tai Solarin Federal University of Education, Ijagun, Ogun State, Nigeria
  • Isaac Adebayo Akinbulu
    Department of Chemistry, University of Lagos, Akoka-Yaba 101245, Lagos State, Nigeria

Keywords:

Alzheimer's disease , 2,3-Dihydroquinazolin-4(1H)-one , , Molecular docking , Density functional theory , Multitarget inhibitors

Abstract

Alzheimer's disease (AD) remains one of the greatest unmet medical needs worldwide and requires a multitarget therapeutic approach as a result of its multifactorial pathogenesis. The 2,3-dihydroquinazolin-4(1H)-one scaffold is a pharmacologically privileged drug known to possess neuroprotective, antioxidant, and enzyme-inhibitory activities that are relevant to AD. Six structurally diverse derivatives (3a, 3k, 3m, 3n, 3r, and 3u) were computationally investigated against three important enzymes associated with AD (acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase 1 (BACE1)). Molecular electrostatic potential maps, quantum chemical reactivity descriptors, and frontier molecular orbital analysis were calculated via the density functional theory (DFT) method at the M062X/def2TZVP level. The molecular docking was done using the Glide program of Maestro against co-crystallized protein structures (PDB: 7E3H, 7AIY, 5HU1) with Rivastigmine and Verubecestat as reference drugs. DFT analysis showed that compound 3n is the most chemically reactive compound with a HOMO–LUMO gap of 6.51 eV, and compound 3r is the most electrophilic with ω = 2.40 eV. The molecular docking revealed that 3k showed the highest binding affinity towards all three targets (AChE: −11.22 kcal/mol, BChE: −8.17 kcal/mol, BACE1: −7.78 kcal/mol) as compared to Rivastigmine (AChE: −6.66 kcal/mol, BChE: −5.21 kcal/mol). Analysis of interactions indicated that aromatic π–π stacking and hydrogen bonding are the predominant types of interactions involved in the binding of AChE, hydrophobic interactions are predominant in the binding of BChE, and polar interactions are predominant in the binding of BACE1. These results identify 3k as a potential multitarget agent that requires further experimental studies

Dimensions

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Published

2026-06-29

How to Cite

Computational Investigation of 2,3-Dihydroquinazolin-4(1H)-one Derivatives as Multitarget Anti-Alzheimer Agents: DFT and Molecular Docking Studies against AChE, BChE, and BACE1. (2026). Lafia Journal of Scientific and Industrial Research, 4(2), 42-59. https://doi.org/10.62050/ljsir2026.v4n2.876

Issue

Volume 4, Issue 2 (October, 2026), Lafia Journal of Scientific and Industrial Research (LJSIR)

Section

Physical Sciences
Copyright & Licensing

Copyright (c) 2026 Abosede Adejoke Badeji, Olalekan Samuel, Segun D. Oladipo, Adejoke D. Osinubi, Adetoro A. Osanyinbi, Isaac Adebayo Akinbulu (Author)

Creative Commons License

This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

How to Cite

Computational Investigation of 2,3-Dihydroquinazolin-4(1H)-one Derivatives as Multitarget Anti-Alzheimer Agents: DFT and Molecular Docking Studies against AChE, BChE, and BACE1. (2026). Lafia Journal of Scientific and Industrial Research, 4(2), 42-59. https://doi.org/10.62050/ljsir2026.v4n2.876

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