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Title: Synthesis and characterization of novel multifunctional ligands aiming at symptoms and causes of Alzheimer's disease

Author:

Wichur, Tomasz

Date:

2020

Type:

Praca doktorska

Abstract:

The research described in the thesis includes the design of new multifunctional compounds with potential application in the therapy of Alzheimer's disease, their synthesis, spectra characteristics and analysis of results of in vitro and in silico tests. The first group of ligands are beta-secretase and cholinesterase inhibitors with anti-aggregating properties against amyloid beta (Aβ) and tau protein, while the second group comprises compounds combining 5-HT6 receptor antagonism with cholinesterase inhibitory activity. Structural modifications aimed at optimization of activity towards biological targets of interest and - in the case of the second group - improvement of physicochemical parameters. The compounds were synthesized using specially developed synthetic routes, and their biological activity was assessed in the following assays: Ellman's (cholinesterase inhibition), FRET-based (inhibition of betasecretase), thioflavin T / S in vitro and in cellulo (Aβ and tau aggregation), FRAP and ABTS (antioxidant properties) and radio ligand binding assay. The analysis of the obtained results allowed the identification of a number of new, compounds with a multidirectional mechanism of action, which are an excellent starting point for further research on the application of multifunctional ligands m the treatment of Alzheimer's disease.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

farmacja

Degree grantor:

Rada Dyscypliny Nauki farmaceutyczne

Promoter:

Więckowska, Anna

Date issued:

2020

Identifier:

oai:dl.cm-uj.krakow.pl:4441

Call number:

ZB-132232

Language:

eng; pol

Access rights:

tylko w bibliotece

Subject and keywords:

multifunctional ligands Alzheimer's disease cholinesterase inhibitors 5-HT6 receptor antagonists beta amyloid and tau protein aggregation inhibitors

Object collections:

Last modified:

Mar 25, 2024

In our library since:

Jan 20, 2022

Number of object content hits:

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Number of object content views in PDF format

0

All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/4442

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Edition name Date
ZB-132232 Mar 25, 2024

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