First Examples of H₂S-Releasing Glycoconjugates: Stereoselective Synthesis and Anticancer Activities

Abstract

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 portions 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 anticancer 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.