First examples of H2S-releasing glycoconjugates: stereoselective synthesis and anticancer activities

H2S-donors are currently emerging as promising therapeutic agents in a wide variety of pathologies, including tumors. Cancer cells are characterized by an enhanced uptake of sugars, such as glucose. Therefore, novel glycoconjugated H2S-donors were synthesized, so that high concentrations of H2S can be selectively achieved therein. Dithiolethione- or isothiocyanate-portions were selected for their well-known H2S-releasing properties in the presence of biological substrates. A synthetic procedure employing trichloroacetimidate glycosyl donors was applied to produce, in a stereoselective fashion, C1-glycoconjugates, whereas C6-glycoconjugates were obtained by a Mitsunobu-based transformation. The resulting molecules were then tested for their anti-cancer effects on human pancreas adenocarcinoma ascites metastasis cell line AsPC-1. The most potent inhibitors of cell viability (6aβ and 7b) proved to release H2S inside the AsPC-1 cells and to alter the basal cell cycle.