The Evaluation of Glyceryl C3-Azolyl-Thiogalactosides as Galectin-1 and Galectin-3 Ligands.

Autor: Prouza V; University of Chemistry and Technology Prague Faculty of Food and Biochemical Technology: Vysoka skola chemicko-technologicka v Praze Fakulta potravinarske a biochemicke technologie, Department of Chemistry of Natural Compounds, Technická 5, 16628, Prague, CZECHIA., Zýka J; University of Chemistry and Technology Prague Faculty of Food and Biochemical Technology: Vysoka skola chemicko-technologicka v Praze Fakulta potravinarske a biochemicke technologie, Department of Chemistry of Natural Compounds, Technická 5, 16628, Prague, CZECHIA., Kozák J; Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences: Ustav organicke chemie a biochemie Akademie ved Ceske republiky, Biochemical Pharmacology, Flemingovo nám. 2, 16000, Prague, CZECHIA., Magdolenová A; Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences: Ustav organicke chemie a biochemie Akademie ved Ceske republiky, Biochemical Pharmacology, Flemingovo nám. 2, 16000, Prague, CZECHIA., Pohl R; Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences: Ustav organicke chemie a biochemie Akademie ved Ceske republiky, NMR Spectroscopy, Flemingovo nám. 2, 16000, Prague, CZECHIA., Parkan K; University of Chemistry and Technology Prague Faculty of Food and Biochemical Technology: Vysoka skola chemicko-technologicka v Praze Fakulta potravinarske a biochemicke technologie, Department of Chemistry of Natural Compounds, Technická 5, 166 28, Prague 6, CZECHIA.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2024 Dec 14, pp. e202400826. Date of Electronic Publication: 2024 Dec 14.
DOI: 10.1002/cmdc.202400826
Abstrakt: Galectins are a family of galactoside-binding proteins involved in various pathophysiological processes, which makes them attractive targets for drug discovery. The derivatization of d-galactose at C3 and C1 positions has been shown to increase the affinity of synthetic galectin antagonists. In this study, two small libraries of d-galactose derivatives have been designed and synthesized. The first series involved the development of novel aromatic 3-azolyl-3-deoxy-d-galactopyranoses. The second series consisted of epimeric analogs of glyceryl β-S-d-galactopyranosides, which were also derivatized. Binding-affinity evaluations for galectin-1 and galectin-3 have revealed that galactose analogs from both series have potential for further optimization. Notably, a combination of modifications at the C3 position of the galactose ring and on the aglycone has led to the identification of promising galectin inhibitors, specifically the compounds 29R and 32S.
(© 2024 Wiley‐VCH GmbH.)
Databáze: MEDLINE
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