New Thienopyridine Scaffold as An Antidementia Lead: In Silico Study and Biological Screening

Abstract New thienopyridine tacrine analogues were efficiently synthesized. Series 2 and 4 enclosed fourteen new compounds. They were screened against their acetyl cholinesterase, butyryl cholinesterase and β-amyloid protein inhibition. In acetyl cholinesterase inhibition assay, 2h showed IC50 value 26.4 ± 0.03 ng/mL excelling tacrine itself. 2e possessed excellent IC50 values 1.7 ± 0.07 and 14.7 ± 0.03 ng/mL for both the butyryl cholinesterase and β-amyloid protein inhibition assays, sequentially. The in silico ADME studies were investigated for the promising members (2c, 2d, 2e, 2h, 2i, and 4e) and all the results were illustrated. A comparative docking study was conducted between the promising members and both tacrine and donepezil in both acetyl and butyryl choline active sites. The results revealed extra binding patterns.