Synthesis and anti-proliferative activity of 2-hydroxy-1,2-dihydroacronycine glycosides

Purpose. Combination of the acronycine pharmacophore with various sugar units appeared of interest, since numerous anticancer agents possess a sugar moiety, which strongly influence both their bioavailability and their selective toxicity towards tumor cells. Methods. A series of 2-hydroxy-1,2-dihydroacronycine glycosides were synthetized, by condensation of the racemic aglycone with appropriate glycoside donors. Their effect on the inhibition of L1210 cell proliferation were evaluated. Results. Compounds 6a, 6b, 11a, 11b, and 12a, 12b, including a halogenated sugar moiety displayed activities of the same order of magnitude as acronycine itself. Compounds 7a, 7b, and 8a, 86, bearing a 2,3,6-trideoxy-3-azido-L-lyxo- and L-arabino-hexopyranose unit respectively, were significantly more potent than acronycine in inhibiting cell proliferation. Conclusions. The activity of 2-hydroxy-1,2-dihydroacronycine glycosides seems to be related to the lipophilicity of the sugar unit.