Synthesis and Structure Identification of a Group of Tacrine Derivatives as Potential Acetylcholinesterase Inhibitors
Project no. 271 · Status: Kapanmış · 2016
Summary
In this study a group of tacrine derivatives which are considered to be effective for Alzheimer’s disease by inhibiting the acetylcholinesterase (AChE) enzyme were designed and synthesized. The title compounds were synthesized in three steps. In the first step, anthranilic acid and cyclohexanone were reacted with POCl3 to obtain 9-chloro-1,2,3,4-tetrahydroacridine. Aromatic nucleophilic substitution of 9-chloro-1,2,3,4-tetrahydroacridine with hydrazine hydrate gave 9-hydrazinyl-1,2,3,4-tetrahydroacridine. In the final step of the synthesis, 9-hydrazinyl-1,2,3,4- tetrahydroacridine ring condensed with nonsubstitüted- and para substituted aromatic aldehydes. All title compounds were purified and their molecule structures were identified by IR, 1H NMR, ESI-MS spectroscopic methods. The inhibitory potency against AChE was investigated by a modified colorimetric Ellman’s test. According to the AChE inhibitory activity results, all of the title compounds exhibited good inhibition in the range of IC50= 0.088-0.359 µM. Among the tested compounds, the most active compound found to be 9-(2-(4-methylbenzylidene)hydrazinyl)-1,2,3,4-tetrahydroacridine (G2) having IC50 value of 0.088 µM. Keywords: Acethylcholinesterase Inhibitors, Anti-Alzheimer Compounds, Tacrine Derivatives