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.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► 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.