Design, synthesis and biological evaluation of betulin-3-yl 2-amino-2-deoxy-β-D-glycopyranosides

Abstract Betulin is a natural pentacyclic triterpenoid, possessing a lupane-structure, with a wide range of pharmacological activities. Its weak hydrosolubility hinders the biological activity of the compound and its derivatives. To circumvent this problem, we synthesized and tested in vitro three D-glycosaminosides of betulin. The structure of betulin was modified by incorporation of 2-amino-2-deoxy-D-gluco- and -D-galactopyranosyl moieties to its C-3 position. So far betulinyl glycosides containing these amino-sugars have not been reported in the literature. The structure of the studied derivatives was confirmed by 1H and 13C NMR spectroscopy as well as mass spectrometry. The 28-O-acetylbetulin-3-yl 2-amino-2-deoxy-β-D-glucopyranoside and betulin-3-yl 2-amino-2-deoxy-β-D-gluco- and β-D-galactopyranoside were tested against the human pathogenic fungi and Gram-positive and Gram-negative bacteria. Moreover, the MTT assay of their cytotoxicity was performed on the MCF-7 breast cancer cell line and on the HDFa, human dermal fibroblasts. The Ames test on mutagenic properties completed our biological assays.