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Design, synthesis and biological evaluation of novel N-phosphorylated and O-phosphorylated tacrine derivatives as potential drugs against Alzheimer’s disease
Abstract
In this work, we designed, synthesised and biologically investigated a novel series of 14N- and O-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 6–13 and 16–21 that were characterised by 1H, 13 C, 31P 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 8 with an IC50 value of 6.11nM and against BChE 13 with an IC50 value of 1.97 nM and they were 6- and 12-fold potent than tacrine. Compound 19 showed the lack of hepatocytotoxicity in MTT assay.
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Authors (6)
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Kowalski Szymon
- Gdański Uniwersytet Medyczny
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Iwona Inkielewicz-Stępniak
- Gdański Uniwersytet Medyczny
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- Accepted or Published Version
- DOI:
- Digital Object Identifier (open in new tab) 10.1080/14756366.2022.2045591
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- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
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JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
no. 37,
pages 1012 - 1022,
ISSN: 1475-6366 - Language:
- English
- Publication year:
- 2022
- Bibliographic description:
- Przybyłowska M., Dzierzbicka K., Szymon K., Demkowicz S., Daśko M., Inkielewicz-Stępniak I.: Design, synthesis and biological evaluation of novel N-phosphorylated and O-phosphorylated tacrine derivatives as potential drugs against Alzheimer’s disease// JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY -Vol. 37,iss. 1 (2022), s.1012-1022
- DOI:
- Digital Object Identifier (open in new tab) 10.1080/14756366.2022.2045591
- Sources of funding:
-
- COST_FREE
- Verified by:
- Gdańsk University of Technology
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