Researchers are paying increasing attention to the strongly negatively charged heteropolysaccharides in cells, in the extracellular matrix or in the cell wall. Examples of such molecules are glycosaminoglycans (e.g., heparin, heparan sulphate). It is well known from the literature that heparin and its derivatives have anti-inflammatory, angiogenic, metastatic and growth factor inhibitory activity. Herein, we present the efficient synthesis of six non-glycosaminoglycan (Glc-GlcA-Glc-sequenced) and one heparin-related (GlcN-GlcA-Glc-sequenced) trisaccharides with various functional group patterns. The anti-inflammatory, antioxidant and cell growth-inhibitory/cytotoxic effects of the synthesized compounds were tested. Among the investigated molecules, we have found some derivatives with a promising anti-inflammatory and antioxidant effect.

Glycosaminoglycans (GAGs) are linear, high molecular weight polydisperse heteropolysaccharides consisting of repeating disaccharide units, which always contain a uronic acid building block (e.g., d-glucuronic acid or l-iduronic acid). Their analogues containing d-mannuronic acid were not known until now. Another important class of the linear negatively charged polisaccharides are alginates, which are also present in the cell surface in the cell wall. They are composed of blocks of 1,4-linked β-d-mannuronic acid and its C-5 epimer α-l-guluronic acid in alternating or random order. Both groups of molecules have significant biological activity (e.g., cell growth inhibitory activity, anti-inflammatory effect, etc.). In the course of our research, we combined the structural characteristics of these two groups of molecules and produced a series of heparan sulphate analogue trisaccharides containing d-mannuronic acid, with a simplified structure, in which α- and β-mannosidic bonds are also found. Since trisaccharides may exert diverse biological effects and alginate derivatives can influence wound healing processes, we investigated the effects of the synthesized compounds on primary human dermal fibroblasts. We found that, when applied at 10 μM, none of the compounds influenced viability or spontaneous collagen production; however, some derivatives exhibited anti-inflammatory activity and suppressed the poly(I:C)-induced release of interleukin 6.