Issue 16, 2019

Hybrid ligands with calixarene and thiodigalactoside groups: galectin binding and cytotoxicity

Abstract

Galectins have diverse functions and are involved in many biological processes because of their complex intra- and extracellular activities. Selective and potent inhibitors for galectins will be valuable tools to investigate the biological functions of these proteins. Therefore, we describe here the synthesis of galectin inhibitors with a potential “chelate effect”. These compounds are designed to bind to two different binding sites on galectins simultaneously. In this paper a series of asymmetric “hybrid” compounds are prepared, which combine two galectin ligands (1) a substituted thiodigalactoside derivative and (2) an antagonist calixarene-based therapeutic agent. NMR spectroscopy was used to evaluate the interactions of these compounds with Galectin-1 and -3. In addition, cellular experiments were conducted to compare the cytotoxic effects of the hybrids with those of a calixarene derivative. While only the thiodigalactoside part of the hybrids showed strong binding, the calixarene part was responsible for observed cytoxoxicity effects, suggesting that the calixarene moiety may also be addressing a non-galectin target.

Graphical abstract: Hybrid ligands with calixarene and thiodigalactoside groups: galectin binding and cytotoxicity

Supplementary files

Article information

Article type
Research Article
Submitted
26 jun 2019
Accepted
08 jul 2019
First published
12 jul 2019
This article is Open Access
Creative Commons BY-NC license

Org. Chem. Front., 2019,6, 2981-2990

Hybrid ligands with calixarene and thiodigalactoside groups: galectin binding and cytotoxicity

H. Zhang, H. Ippel, M. C. Miller, T. J. Wong, A. W. Griffioen, K. H. Mayo and R. J. Pieters, Org. Chem. Front., 2019, 6, 2981 DOI: 10.1039/C9QO00810A

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