Design and synthesis of novel 3-triazolyl-1-thiogalactosides as galectin-1, -3 and -8 inhibitors. Issue 29 (30th June 2022)

• Record Type: Journal Article
• Authors: van Klaveren, Sjors; Dernovšek, Jaka; Jakopin, Žiga; Anderluh, Marko; Leffler, Hakon; Nilsson, Ulf J.; Tomašič, Tihomir
• Is Part Of: RSC advances. Volume 12:Issue 29(2022)
• Page Start: 18973
• Page End: 18984
• Publication Date: 2022-06-30
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d2ra03163a
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : A new series of potent galectin ligands based on the galactose and triazole moieties was designed and synthesised. Abstract : Galectins are galactoside-binding proteins that play a role in various pathophysiological conditions, making them attractive targets in drug discovery. We have designed and synthesised a focused library of aromatic 3-triazolyl-1-thiogalactosides targeting their core site for binding of galactose and a subsite on its non-reducing side. Evaluation of their binding affinities for galectin-1, -3, and -8N identified acetamide-based compound 36 as a suitable compound for further affinity enhancement by adding groups at the reducing side of the galactose. Synthesis of its dichlorothiophenyl analogue 59 and the thiodigalactoside analogue 62 yielded promising pan-galectin inhibitors.