Preparation and functional analysis of gossypols having two carbohydrate appendages with enaminooxy linkages

We developed new gossypol (Gos)-based glycoconjugates through dehydration condensation of native Gos and chemically modified glycosides having aminooxy groups. The resultant glycoconjugates (glycoGos) were resistant to hydrolysis, although they were light-sensitive and slowly decomposed even under indoor lighting. The glycoGos also exhibited improved water solubility compared with native Gos, but their saturated concentrations in water were still low (6.4–17 μM), due to their hydrophobic naphthyl rings. We also carried out WST-8 assays to assess the anticancer activity of the glycoGos on DLD-1 and HepG2 cells and found that the glycoGos having β-lactosides and having β-galactosides (specific ligands for asialoglycoprotein receptors) showed enhanced anticancer activity on HepG2 cells. [Display omitted] •We synthesized gossypol-based glycoconjugates (glycoGos).•The glycoGos were resistant to hydrolysis but light-sensitive.•The glycoGos have improved water solubility in comparison with native Gos.•Some of the glycoGos exhibited enhanced anticancer activity on HepG2 cells.