期刊
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
卷 37, 期 1, 页码 1012-1022出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/14756366.2022.2045591
关键词
Alzheimer's disease; tacrine; phosphorus tacrine analogs; molecular docking; hepatotoxicity; neurotoxicity; cholinesterase inhibitory activity
资金
- Gdansk University of Technology [DS/033171]
- Medical University Gdansk [St-54]
In this study, a series of N- and O-phosphorylated tacrine derivatives were designed, synthesized, and biologically investigated. The results suggest that some of these derivatives have potential anti-Alzheimer's disease properties.
In this work, we designed, synthesised and biologically investigated a novel series of 14 N- 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 H-1, C-13 , P-31 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 6.11 nM 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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