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

被引:8
作者
Dominska, Monika [1 ,2 ]
Pastuch-Gawolek, Gabriela [1 ,2 ]
Dominski, Adrian [3 ]
Kurcok, Piotr [3 ]
Erfurt, Karol [4 ]
机构
[1] Silesian Tech Univ, Dept Organ Chem Bioorgan Chem & Biotechnol, B Krzywoustego 4, PL-44100 Gliwice, Poland
[2] Silesian Tech Univ, Biotechnol Ctr, B Krzywoustego 8, PL-44100 Gliwice, Poland
[3] Polish Acad Sci, Ctr Polymer & Carbon Mat, M Curie Sklodowskiej 34, PL-41819 Zabrze, Poland
[4] Silesian Tech Univ, Dept Chem Organ Technol & Petrochem, B Krzywoustego 4, PL-44100 Gliwice, Poland
来源
MOLECULES | 2022年 / 27卷 / 03期
关键词
quinoline glycoconjugates; metabolites; cytotoxicity; anticancer activity; click chemistry; TISSUE TRACE-ELEMENTS; GLUCOSE TRANSPORTERS; BREAST-CANCER; COPPER; 8-HYDROXYQUINOLINE; NANOCARRIERS; EXPRESSION; STRATEGIES; COMPLEXES; CHEMISTRY;
D O I
10.3390/molecules27031040
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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.
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页数:21
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