School of Chemistry, National University of Ireland, Galway, Ireland.
Eur J Med Chem. 2010 Sep;45(9):3762-9. doi: 10.1016/j.ejmech.2010.05.025. Epub 2010 May 19.
A facile 6-exo-trig cyclization of sigma-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 microM. 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.
σ-芳基自由基的简便 6-endo-trig 环化反应能够合成各种芳环稠合的苯并咪唑和苯并咪唑醌。最具高度共轭的萘基稠合苯并咪唑醌（(5-甲基-5,6-二氢苯并咪唑并[2,1-a]苯并[f]异喹啉-8,11-二酮）对人宫颈（HeLa）和前列腺（DU145）癌细胞系具有最高的特异性，在小于 1 microM 的剂量下对人正常（GM00637）细胞系的毒性很小。相比之下，2-芳环取代的（苯并咪唑-4,7-二酮）类似物，具有吡啶环的苯并咪唑醌和丝裂霉素 C 对正常细胞系的毒性比高度共轭的萘基稠合苯并咪唑醌更大。
