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- Title
Thiol-ene "Click" Synthesis and Pharmacological Evaluation of C-Glycoside sp2-Iminosugar Glycolipids.
- Authors
Sánchez-Fernández, Elena M.; García-Moreno, M. Isabel; García-Hernández, Raquel; Padrón, José M.; García Fernández, José M.; Gamarro, Francisco; Ortiz Mellet, Carmen; Díez, David; Castro, María Ángeles
- Abstract
The unique stereoelectronic properties of sp2-iminosugars enable their participation in glycosylation reactions, thereby behaving as true carbohydrate chemical mimics. Among sp2-iminosugar conjugates, the sp2-iminosugar glycolipids (sp2-IGLs) have shown a variety of interesting pharmacological properties ranging from glycosidase inhibition to antiproliferative, antiparasitic, and anti-inflammatory activities. Developing strategies compatible with molecular diversity-oriented strategies for structure–activity relationship studies was therefore highly wanted. Here we show that a reaction sequence consisting in stereoselective C-allylation followed by thiol-ene "click" coupling provides a very convenient access to α-C-glycoside sp2-IGLs. Both the glycone moiety and the aglycone tail can be modified by using sp2-iminosugar precursors with different configurational profiles (d-gluco or d-galacto in this work) and varied thiols, as well as by oxidation of the sulfide adducts (to the corresponding sulfones in this work). A series of derivatives was prepared in this manner and their glycosidase inhibitory, antiproliferative and antileishmanial activities were evaluated in different settings. The results confirm that the inhibition of glycosidases, particularly α-glucosidase, and the antitumor/leishmanicidal activities are unrelated. The data are also consistent with the two later activities arising from the ability of the sp2-IGLs to interfere in the immune system response in a cell line and cell context dependent manner.
- Subjects
GLYCOLIPIDS; STRUCTURE-activity relationships; CELL lines; CARBOHYDRATES; IMMUNE system; GLYCOSIDASE inhibitors
- Publication
Molecules, 2019, Vol 24, Issue 16, p2882
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules24162882