Thieno[2,3-d]pyrimidines as Novel Scaffolds for Acetylcholinesterase Inhibitors: Synthesis, Biological Activity, and Molecular Studies

Fahmy, Nourhan Magdi; Basiony, Ebtesam A; Abdel-Rahman, Adel A-H; Hassan, nasser A

doi:10.21608/ejchem.2025.394718.11912

	Thieno[2,3-d]pyrimidines as Novel Scaffolds for Acetylcholinesterase Inhibitors: Synthesis, Biological Activity, and Molecular Studies
Egyptian Journal of Chemistry
Articles in Press, Accepted Manuscript, Available Online from 30 July 2025
Document Type: Original Article
DOI: 10.21608/ejchem.2025.394718.11912
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Authors
Nourhan Magdi Fahmy ¹; Ebtesam A Basiony²; Adel A-H Abdel-Rahman ³; nasser A Hassan ⁴
¹Monufia university , faculty of science
²Department of Chemistry,Faculty of Science, Menofia University,Shibin El-Kom
³Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koam, EGYPT.
⁴NRC
Abstract
inhibitory activity as potential anti-Alzheimer’s agents. The synthesized compounds were characterized through various spectroscopic techniques. Improved activity was observed in molecules containing hydrogen-bond donors and electron-donating moieties, as indicated by SAR findings. Compound 6 showed the highest potency with an IC50 of 0.199 µM. Molecular docking studies demonstrated strong π–π stacking and hydrogen bonding interactions between 6 and key residues in the AChE active site. In silico ADME profiling confirmed drug-like properties in accordance with Lipinski’s rule of five. These results suggest thieno[2,3-d]pyrimidines as promising scaffolds for the development of novel AChE inhibitors.
Keywords
Thieno[2,3-d]pyrimidine; phosgene-iminium chloride; anti-Alzheimer'; s activity; molecular docking; molecular dynamics


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