Russian Journal of General Chemistry. Vol. 92, No. 11, Pages 2259-2266, 2022

M. V. Grishchenko^a, N. A. Elkina^a, G. F. Makhaeva^b, Ya. V. Burgart^a, N. P. Boltneva^b, E. V. Rudakova^b, E. V. Shchegolkov^a, N. V. Kovaleva^b, O. G. Serebryakova^b, and V. I. Saloutin^a^,*

^aPostovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, Yekaterinburg, 620990 Russia

^bInstitute of Physiologically Active Compounds at Federal Research Center of Problem of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Chernogolovka, 142432 Russia

Abstract— The condensation of tacrine aminopolymethylene derivatives with diethyl (ethoxymethylidene)malonate led to the new hybrid compounds—conjugates, which were the effective inhibitors of acetylcholinesterase (AChE) (IC₅₀ up to 0.538 μM) and butyrylcholinesterase (IC₅₀ up to 0.0314 μM). They can displace propidium iodide from peripherical anionic site of AChE at the level of the reference drug donepezil and demonstrate a weak antioxidant activity. Conjugates are of interest for further extended research as potential drugs for the Alzheimer’s disease treatment.

Keywords: conjugate, tacrine, diethylmalonate, anticholinesterase activity, propidium displacement

Conjugates of Tacrine with Aminomethylidene-Substituted Malonates: Synthesis and Biological Evaluation