Studies on quinones. Part 41: Synthesis and cytotoxicity of isoquinoline-containing polycyclic quinones

In the search for new potentially anticancer drugs, isoquinolinequinone-containing polycyclic compounds have been designed and synthesized through highly regiocontrolled cycloaddition reactions of methyl 1,3-dimethyl-5,8-dioxo-5,8-dihydroisoquinoline-4-carboxylate with polarized 1,3-dienes and a thiazole-o-quinodimethane. The new N-heterocyclic quinones were tested on normal human fibroblasts and four distinct human cancer cell lines. Two of the evaluated compounds displayed significant in vitro activity (IC50: 0.44–5.9 μM) comparable to that of the reference drug etoposide.

The regioselective synthesis of fused isoquinolinequinones (i.e., 6, 8, 13, and 15) through highly regiocontrolled cycloaddition reactions from methyl 1,3-dimethyl-5,8-dioxo-5,8-dihydroisoquinoline-4-carboxylate 3 and 1,3-dienes is reported. The 2-aza- and 1,6-diaza-anthraquinone derivatives displayed significant in vitro activity on normal fibroblast and four tumor cell lines.Figure optionsDownload as PowerPoint slide