8-Hydroxyquinoline Glycoconjugates Containing Sulfur at the Sugar Anomeric Position-Synthesis and Preliminary Evaluation of Their Cytotoxicity.

Monika Krawczyk,Karol Erfurt,Gabriela Pastuch-Gawołek,Agnieszka Hadasik

doi:10.3390/molecules25184174

Monika Krawczyk, Karol Erfurt + Show 2 more

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https://doi.org/10.3390/molecules25184174

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Abstract

One of the main factors limiting the effectiveness of many drugs is the difficulty of their delivery to their target site in the cell and achieving the desired therapeutic dose. Moreover, the accumulation of the drug in healthy tissue can lead to serious side effects. The way to improve the selectivity of a drug to the cancer cells seems to be its conjugation with a sugar molecule, which should facilitate its selective transport through GLUT transporters (glucose transporters), whose overexpression is seen in some types of cancer. This was the idea behind the synthesis of 8-hydroxyquinoline (8-HQ) derivative glycoconjugates, for which 1-thiosugar derivatives were used as sugar moiety donors. It was expected that the introduction of a sulfur atom instead of an oxygen atom into the anomeric position of the sugar would increase the stability of the obtained glycoconjugates against untimely hydrolytic cleavage. The anticancer activity of new compounds was determined based on the results of the MTT cytotoxicity tests. Because of the assumption that the activity of this type of compounds was based on metal ion chelation, the effect of the addition of copper ions on cell proliferation was tested for some of them. It turned out that cancer cells treated with glycoconjugates in the presence of Cu2+ had a much slower growth rate compared to cells treated with free glycoconjugates in the absence of copper. The highest cytotoxic activity of the compounds was observed against the MCF-7 cell line.

Highlights

Despite significant progress in the treatment of various types of diseases, cancer is still one of the most considerable clinical problems
1-thiosugars derivatives were used for the synthesis of quinoline glycoconjugates
Glycoconjugation of quinoline derivatives with appropriately functionalized 1-sugar derivatives was supposed to increase the selectivity of such obtained prodrugs in relation to the cancer cells, thanks to the facilitation of its transport through GLUT transporters, whose overexpression is seen in some types of cancer

Summary

Introduction

Despite significant progress in the treatment of various types of diseases, cancer is still one of the most considerable clinical problems. Anticancer therapies introduced so far are not effective enough. This is due to the low selectivity profile of approved chemotherapeutics, the use of which leads to numerous undesirable side effects. The resistance of cancer cells to available pharmaceuticals results in their rapid proliferation and metastasis [1]. It is necessary to develop new safe drugs that target cancer cells directly without damaging healthy cells. One of the main factors limiting the effectiveness of many drugs is the difficulty of their delivery to their target site in the cell across the phospholipid cell membranes. A better understanding of Molecules 2020, 25, 4174; doi:10.3390/molecules25184174 www.mdpi.com/journal/molecules

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