New saccharide derivatives of indolo[2,3-b]quinoline as cytotoxic compounds and topoisomerase II inhibitors

Abstract

Some of alkyl- and alkylamino- derivatives of 6H-indolo[2,3-b]quinolines are known to be active antiproliferative and cell cycle modulating compounds. Their cytotoxic properties are, at least in part, due to DNA intercalation ability and topoisomerase II inhibition activity. To improve physicochemical and biological properties of 6H-indolo[2,3-b]quinolines the series of new, saccharide (C-2, C-9 or N-6) derivatives were designed and synthesized. The influence of different carbohydrate units (D-glucose, D-lactose, L-rhamnose, Lacosamine, L-daunosamine), position of attachment and linker size on cytotoxic properties and topoisomerase II inhibition activity were tested. Among compounds tested there were 2-deoxy-α-D-glucopyranoside (1-6), 2-deoxy-α-L-rhamnopyranoside (7-12) and 2-deoxy-α-D-lactopyranoside (13-18) derivatives in the group of saccharide moiety containing compounds and a-L-daunosaminide (19-24) and a-L-acosaminide (25- 27) in the aminosaccharide derivatives series as well.