Gold‐Dithiocarbamato Glycoconjugates as Potential Anticancer Agents: Design, Physico‐Chemical Characterization, and In Vitro Biological Activity

To develop new metal-based glycoconjugates as potential anticancer agents, three gold(III)-dithiocarbamato glycoconjugates of the type [AuIIIBr2(SSC-Inp-GlcN)] (Au3-5), their gold(I)-phosphine counterparts [AuI(SSC-Inp-GlcN)(PPh3)] (AuP3-5), and gold(I)-carbene analogs [AuI(SSC-Inp-GlcN)(Et2BzImy)] (AuC3-5) (Inp: isonipecotic moiety; GlcN: amino-glucose scaffold; Et2BzImy: 1,3-diethylbenzimidazol-2-ylidene moiety), as well as the corresponding non-glycosylated counterparts (Au1-2, AuP1-2, and AuC1-2) bearing a terminal ester or amide function, are generated and characterized by means of several analytical techniques (FT-IR, 1H-/13C-NMR, UV–Vis, X-ray crystallography). Their stability under physiologically relevant conditions (phosphate-buffered saline solution) has also been evaluated. Contrary to the gold(III)-glycoconjugates, the glucose-functionalized gold(I) derivatives show a significant antiproliferative effect against colorectal adenocarcinoma (HT-29), metastatic breast adenocarcinoma (MDA-MB-231), and breast adenocarcinoma (MCF-7) cells, with IC50 values in the low micromolar range, the gold(I)-phosphine derivatives turning up to be the best performers. Cell uptake studies show no evident correlation between cell growth inhibition and cellular uptake, and the use of glucose-free cell culture media and a GLUT1 inhibitor rules out the involvement of glucose transporters in cell internalization, thus suggesting alternative cell death pathways such as acting at extracellular level (especially for the gold(I) derivatives).