Design, Synthesis and Biological Evaluation of Novel -phosphorylated and -phosphorylated Tacrine Derivatives As Potential Drugs Against Alzheimer's Disease

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2022 Apr 1

PMID 35361039

Authors

Maja Przybylowska

Krystyna Dzierzbicka

Szymon Kowalski

Sebastian Demkowicz

Mateusz Dasko

Iwona Inkielewicz-Stepniak

Affiliations

Soon will be listed here.

Abstract

In this work, we designed, synthesised and biologically investigated a novel series of 14 - and -phosphorylated tacrine derivatives as potential anti-Alzheimer's disease agents. In the reaction of 9-chlorotacrine and corresponding diamines/aminoalkylalcohol we obtained diamino and aminoalkylhydroxy tacrine derivatives. Next, the compounds were acid to give final products - and - that were characterised by H, C, P NMR and MS. The results of the docking studies revealed that the designed phosphorus hybrids, in theory can bind to AChE and BChE. All compounds exhibited significantly lower AutoDock Vina scores compared to tacrine. The inhibitory potency evaluation was performed using the Ellman's method. The most inhibitory activity against AChE exhibited compound with an IC value of 6.11 nM and against BChE with an IC value of 1.97 nM and they were 6- and 12-fold potent than tacrine. Compound showed the lack of hepatocytotoxicity in MTT assay.

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