Synthesis, Crystal Structure and Biological Evaluation of Novel 2-Phenylthiazole Derivatives as Multi-Targeting Agents to Treat Alzheimer's Disease

Abstract

Three novel 2-phenylthiazole derivatives were synthesised and characterised by spectroscopic techniques. The structure of the synthesised compounds was unambiguously confirmed by a single-crystal X-ray diffraction analysis of ethyl 2-(4-{[5-(4-benzylpiperidin-1-yl)pentyl]oxy}phenyl)thiazole-4-carboxylate. All of the compounds presented good cholinesterase-inhibition activities and ethyl 2-(4-{[5-(4-benzylpiperidin-1-yl)pentyl]oxy}phenyl)thiazole-4-carboxylate showed the best acetylcholinesterase-inhibition and butyrylcholinesterase-inhibition abilities with IC50 values of 5.19 μM and 5.83 μM. The docking study demonstrated that it could interact with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of acetylcholinesterase and could chelate with metal ions like Cu2+ and Zn2+.

Synthesis, Crystal Structure and Biological Evaluation of Novel 2-Phenylthiazole Derivatives as Butyrylcholinesterase Inhibitors

“…[4][5][6] We have previously synthesised a series of 2-phenylthiazole derivatives and found that these derivatives possess AChE-and BuChE-inhibiton activities. 7,8 In this study, three novel 2-phenylthiazole derivatives were synthesised and characterised by NMR and single-crystal X-ray diffraction analysis. The role of intermolecular interactions in these compounds was analysed through single-crystal structure studies.…”