Abstract
A series of N-alkylated and N-benzylated thiazole-4-carboxylates (3a-n) were prepared via alkylation/benzylation of ethyl 2-(2-(arylidene)hydrazinyl)thiazole-4-carboxylates (1) . The structures of all synthesized thiazoles were established with FT-IR, H-1-, C-13-NMR and HRMS spectroscopic techniques. All synthesized compounds were screened as inhibitors of acetylcholinesterase (AChE), using galanthamine as the standard. The AChE activity results revealed, that the compounds ethyl 2-(2-(4-methoxybenzylidene)(benzyl)hydrazinyl)thiazole-4-carboxylate (3n) and ethyl 2-(2-(4-methylbenzylidene)(decyl)hydrazinyl)thiazole-4-carboxylate (3k) were moderate inhibitor with IC50 values 9.56 +/- 2.76 and 9.92 +/- 0.96 mu M, (better than the standard). Simulation studies based on virtual screening of AChE inhibition by molecular docking predicted the binding free energies and molecular inhibition of 3f, 3k and 3n compounds (Delta G = -7.73, Delta G = -7.91 and Delta G = -8.13) was comparable with galanthamine. These three compounds occupied the same binding cavity as galanthamine, with greater affinity. Furthermore, in silico, all other compounds also exhibited moderate to good AChE inhibition activities. (C) 2021 Elsevier B.V. All rights reserved.