Structure-Guided Design of <scp>d</scp>-Galactal Derivatives with High Affinity and Selectivity for the Galectin-8 N-Terminal Domain
Mujtaba Hassan, Floriane Baussière, Samo Guzelj, Anders Sundin, M. Håkansson, Rebeka Kovačič, Hakon Leffler, Tihomir Tomašič, Marko Anderluh, Žiga Jakopin, Ulf J. Nilsson
Abstract
-tetrazolium) (MTS) assay evaluation of the d-galactal-benzimidazole hybrid and an analogous galactoside derivative on a panel of cell lines with MTS assay showed no effect on cell viability up to 100 μM concentration. A subsequent functional assay using the MDA-MB-231 cell line demonstrated that the d-galactal-benzimidazole hybrid and the analogous galactoside derivative reduced the secretion of the proinflammatory cytokines interleukin-6 (IL-6) and IL-8 in a dose-dependent manner. Therefore, these compounds represent potential probes for galectin-8N pharmacology investigations and possibly promising leads for the design and synthesis of potent and selective galectin-8 inhibitors as potential antitumor and anti-inflammatory agents.