Synthesis and anticancer activity of aza-quinone glycoconjugates

Quinones fused to N-heterocyclic aromatic rings have been reported in the literature1 as potential anticancer agents. On the basis of our experience in the field of the synthesis and biological evaluation of new quinone-carbohydrate conjugates2 and 1,2,3-triazole derivatives3, we described the synthesis and in vitro anticancer activity studies of compounds 1a-b in which Juglone (2) and 1,2,3-triazole frameworks are directly attached (Figure). The thermal 1,3-dipolar cycloaddition reaction between glycosyl azides and juglone (2) afforded corresponding naphthotriazoles 1a-b, in moderated yields, and unexpected amino-quinone derivatives 3a-b, which possess an aminocarbohydrate chain at the C-2 position of the quinone ring. The in vitro anticancer activity of the compounds 1a-b and 3a-b were assessed against A-549 , HCT-116 and MDA-MB 435 human cancer cell lines. Two derivatives were found to be more active against melanoma cells than the clinically useful anticancer agent doxorubicin (4), and none of the compounds caused mouse erythrocyte lysis.