Synthesis and toxicity towards normal and cancer cell lines of benzimidazolequinones containing fused aromatic rings and 2-aromatic ring substituents

A facile 6-exo-trig cyclization of σ-aromatic radicals has allowed the synthesis of various aromatic ring fused benzimidazoles and benzimidazolequinones. The most highly conjugated naphthyl fused benzimidazolequinone, (5-methyl-5,6-dihydrobenzimidazo[2,1-a]benzo[f]isoquinoline-8,11-dione) showed the highest specificity towards human cervical (HeLa) and prostate (DU145) cancer cell lines with little toxicity towards a human normal (GM00637) cell line at doses of <1 μM. In contrast, 2-aromatic ring substituted (benzimidazole-4,7-diones) analogues, benzimidazolequinone with a pyridine ring and mitomycin C were more toxic than the highly conjugated naphthyl fused benzimidazolequinone towards the normal cell line.

Graphical abstractThe naphthyl fused benzimidazolequinone showed the highest specificity towards human cervical (HeLa) and prostate (DU145) cancer cell lines, with little toxicity towards a human normal (GM00637) cell line at doses of <1 μM.Figure optionsDownload full-size imageDownload as PowerPoint slide