Synthesis and Preliminary Evaluation of the Cytotoxicity of Potential Metabolites of Quinoline Glycoconjugates

Molecules

Piotr Kurcok¹  Adrian Domiński¹  Karol Erfurt²  Monika Domińska³  Gabriela Pastuch-Gawołek³ 

[1] Centre of Polymer and Carbon Materials, Polish Academy of Sciences, M. Curie-Skłodowskiej 34, 41-819 Zabrze, Poland;Department of Chemical Organic Technology and Petrochemistry, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland;Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland;

关键词: quinoline glycoconjugates;    metabolites;    cytotoxicity;    anticancer activity;    click chemistry;   

DOI  :  10.3390/molecules27031040

来源: DOAJ

【 摘 要 】

The design of prodrugs is one of the important strategies for selective anti-cancer therapies. When designing prodrugs, attention is paid to the possibility of their targeting tumor-specific markers such as proteins responsible for glucose uptake. That is why glycoconjugation of biologically active compounds is a frequently used strategy. Glycoconjugates consisting of three basic building blocks: a sugar unit, a linker containing a 1,2,3-triazole ring, and an 8-hydroxyquinoline fragment was described earlier. It is not known whether their cytotoxicity is due to whole glycoconjugates action or their metabolites. To check the biological activity of products that can be released from glycoconjugates under the action of hydrolytic enzymes, the synthetically obtained potential metabolites were tested in vitro for the inhibition of proliferation of HCT-116, MCF-7, and NHDF-Neo cell lines using the MTT assay. Research shows that for the full activity of glycoconjugates, the presence of all three building blocks in the structure of a potential drug is necessary. For selected derivatives, additional tests of targeted drug delivery to tumor cells were carried out using polymer nanocarriers in which they are encapsulated. This approach significantly lowered the determined IC₅₀ values of the tested compounds and improved their selectivity and effectiveness.

【 授权许可】

Unknown