Conjugates of anticholinesterase drugs ipidacrine and tacrine with thiouracils: synthesis and biological properties

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发表日期：

2024年11月1日

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M. V. Grishchenko,
O. G. Khudina,
G. F. Makhaeva,
Ya. V. Burgart,
N. V. Kovaleva,
E. V. Rudakova,
N. P. Boltneva,
M. V. Ulitko,
V. I. Saloutin,
V. N. Charushin

摘要

Chloroalkylene amide derivatives were obtained by acylation of known Cholinesterase inhibitors, ipidacrine and tacrine. The acylated derivatives were used in the alkylation of substituted 2-thiouracils (R = Me, CF₂H, CF₃, (CF₂)₂H)) for the synthesis of new hybrid compounds. Study of the esterase profile revealed a pronounced activity and selectivity of the obtained conjugates against butyrylcholinesterase (IC₅₀ up to 2.03 µmol L⁻¹), moderate displacement of propidium from the acetylcholinesterase peripheral anionic site, and moderate inhibition of the β-amyloid self-aggregation. It was found that conjugation of thiouracils with tacrine leads to a decrease in the hepatotoxicity of the hybrid compounds compared to that of tacrine, while in the case of ipidacrine derivatives, no hepatotoxicity was observed.