Synthesis and identification of novel indolo[2,3-a]pyrimido[5,4-c]carbazoles as a new class of anti-cancer agents

A range of 5,6-bisindole and 5-indole-6-(7-azaindole)pyrimidinones were synthesised via a β-keto ester intermediate and a screen of cyclisation conditions undertaken. The optimised route to this new class of indolocarbazoles and azaindolocarbazoles involved photocyclisation, with typical yields of 50–60%. These derivatives were screened for anti-cancer activity via topo II inhibition and the NCI-60 cell line assay, with the screening indicating a lack of topo II inhibition, but significant in vitro growth inhibition within this new chemical class, in the low micromolar range against renal cancer, melanoma and colon cancer cell lines.

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► New class of indolocarbazoles and azaindolocarbazoles synthesised.
► Use of novel β-keto ester intermediate and photocyclisation route.
►  Optimised route leading to typical yields of 50–60%.
► Significant in vitro growth against renal cancer, melanoma and colon cancer cells.