Design and synthesis of novel 3-triazolyl-1-thiogalactosides as galectin-1, -3 and -8 inhibitors |
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| Authors: | Sjors van Klaveren,Jaka Dernovš ek,Ž iga Jakopin,Marko Anderluh,Hakon Leffler,Ulf J. Nilsson,Tihomir Tomaš ič |
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| Affiliation: | University of Ljubljana, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Aškerčeva cesta 7, 1000 Ljubljana Slovenia.; Centre for Analysis and Synthesis, Department of Chemistry, Lund University, SE-221 00 Lund Sweden.; Department of Laboratory Medicine, Section MIG, Lund University, BMC-C1228b Klinikgatan 28, 221 84 Lund Sweden |
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| 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.A new series of potent galectin ligands based on the galactose and triazole moieties was designed and synthesised. |
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