Structural and computational analysis of a styryl-quinoxaline Alzheimer's therapeutic agent
Inorganica Chimica Acta, vol.599, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 599
- Publication Date: 2026
- Doi Number: 10.1016/j.ica.2026.123240
- Journal Name: Inorganica Chimica Acta
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica, Compendex, Academic Search Ultimate (EBSCO), Engineering Source (EBSCO)
- Ondokuz Mayıs University Affiliated: Yes
Abstract
Quinoxaline derivatives are important scaffolds in drug discovery and neuroprotection. In this work, (E)-3-(4-methoxystyryl)quinoxalin-2(1H)-one (EMQ) was synthesised under solvent-free conditions in high yield (73%), fully characterised, and evaluated as a ligand for a silver(I) complex, [(EMQ)₂Ag₂]. Single-crystal X-ray diffraction revealed a slightly non-planar quinoxaline core engaged in robust N–H⋯O hydrogen bonding and π–π stacking, while DFT (B3LYP/LanL2DZ) calculations indicated a nearly planar, symmetric geometry with an HOMO–LUMO gap of 3.25 eV, consistent with high kinetic stability and favourable charge-transfer characteristics. Molecular docking against acetylcholinesterase (AChE, PDB: 1EVE) showed that EMQ binds within the catalytic gorge with a binding affinity of −7.9 kcal/mol, closely matching Donepezil (−8.4 kcal/mol), and forming key hydrophobic contacts with residues such as Trp84, Tyr121, and Phe330; one-way ANOVA followed by Tukey's post-hoc test confirmed no significant difference between the binding energies of EMQ and Donepezil (p > 0.05). ADMET and in silico toxicity profiling demonstrated full compliance with Lipinski's rules (0 violations) and a low predicted toxicity (non-toxic class in the applied model), supporting EMQ's drug-likeness. Percent buried volume analysis showed that the silver complex exhibits a high %VBur (76.7%), suggesting enhanced steric protection and controlled Ag+ release, which is advantageous for materials stability and potential biomedical deployment. Collectively, these structural, electronic, and computational results position EMQ as a promising acetylcholinesterase inhibitor candidate for Alzheimer's disease and highlight the broader materials-science relevance of its silver(I) complex.