- Synthesis of 8-hydroxyquinoline glycoconjugates and preliminary assay of their β1,4-GalT inhibitory and anti-cancer properties
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8-Hydroxyquinoline scaffold is a privileged structure used in designing a new active agents with therapeutic potential. Its connections with the sugar unit is formed to improve the pharmacokinetic properties. The broad spectrum of activity of quinoline derivatives, especially glycoconjugates, is often associated with the ability to chelate metal ions or with the ability to intercalate into DNA. Simple and effective methods of synthesis glycoconjugates of 8-hydroxyquinoline and 8-hydroxyquinaldine derivatives, containing an O-glycosidic bond or a 1,2,3-triazole linker in their structure, have been developed. The obtained glycoconjugates were tested for their ability to inhibit β-1,4-Galactosyltransferase, as well as inhibit cancer cell proliferation. It was found that used glycoconjugation strategy influenced both improvement of activity and improvement of the bioavailability of 8-HQ derivatives. Their activity depends on type of attached sugar, presence of protecting groups in sugar moiety and presence of a linker between sugar and quinolone aglycone.
- Krawczyk, Monika,Pastuch-Gawolek, Gabriela,Mrozek-Wilczkiewicz, Anna,Kuczak, Michal,Skonieczna, Magdalena,Musiol, Robert
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- Gluconjugates of 8-hydroxyquinolines as potential anti-cancer prodrugs
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8-Hydroxyquinolines are systems of great interest in the field of inorganic and bioinorganic chemistry. They are metal-binding compounds and are known to exhibit a variety of biological activities, such as antibacterial and anticancer activities. Among these systems, clioquinol has been the focus of a renewed interest in recent years. In this scenario, we synthesized and characterized the new clioquinol glucoconjugate, 5-chloro-7-iodo-8-quinolinyl-β-d- glucopyranoside in order to compare this system to that of clioquinol. We also synthesized, 8-quinolinyl-β-d-glucopyranoside, an 8-hydroxyquinoline glucoconjugate. The reason for the development of glucoconjugates is the glucose avidity, and the over-expression of glucose transporters in cancer cells. Here we demonstrate that glycoconjugates are cleaved in vitro by β-glucosidase and these systems exhibit antiproliferative activity against different tumor cell lines in the presence of copper(ii) ions.
- Oliveri, Valentina,Giuffrida, Maria Laura,Vecchio, Graziella,Aiello, Cinzia,Viale, Maurizio
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