Akademik Veri Yönetim Sistemi
POLYCYCLIC AROMATIC COMPOUNDS, 2026 (SCI-Expanded, Scopus)
While dual cholinesterase (AChE/BChE) inhibitors are urgently needed for Alzheimer's disease (AD) management, finding effective multi-target agents remains challenging. To address this, we designed and synthesized a novel series of thiazole-bearing compounds and evaluated their dual anticholinesterase and antioxidant potentials. The antioxidant capacities were tested via CUPRAC, FRAP, and DPPH assays, revealing compounds 1 and 8 as the most active derivatives with DPPH IC50 values of 62.510 +/- 0.027 mu M and 65.190 +/- 0.025 mu M, respectively]. For ChE inhibition, compound 3 emerged as a highly potent dual competitive inhibitor, outperforming the standard drug donepezil, with IC50 values of 1.440 mu M for AChE and 3.620 mu M for BChE. In silico studies elucidated the molecular basis of this activity; induced-fit docking revealed strong binding affinities for compound 3 with Glide scores of -9.82 kcal/mol (AChE) and -10.76 kcal/mol (BChE). Subsequent 500 ns molecular dynamics (MD) simulations confirmed the stability of these complexes, exhibiting low average protein RMSD values (2.25 & Aring; for AChE; 2.19 & Aring; for BChE) and highly favorable average MM/GBSA binding free energies (Delta Gbind) of -68.81 kcal/mol and -61.82 kcal/mol, respectively. Additionally, DFT calculations (MEP and FMO) were performed to elucidate the electronic properties correlating with the bioactivity. This study presents a novel thiazole scaffold as a promising lead for developing effective multi-target agents against AD.