The influence of the aziridinyl substituent of benzimidazoles and benzimidazolequinones on toxicity towards normal and Fanconi anaemia cells

Aziridinyl substituted benzimidazolequinones are more toxic than methoxy analogues towards normal human fibroblast cells (GM00637). The aziridinyl substituent is required for hypersensitive killing of Fanconi anaemia (FA) cells (PD20i) deficient in FANCD2. Despite lacking quinone functionality, 4,7-dimethoxy-N-[(aziridin-2-yl)methyl]benzimidazole also induces hypersensitivity from FA cells, similar to their response towards mitomycin C. Expression of FANCD2 (in PD20:RV) corrects FA cell hypersensitivity supporting cellular response via the FANC pathway.

Graphical abstractDespite lacking the quinone functionality required for bioreduction, 4,7-dimethoxy-N-[(aziridin-2-yl)methyl]benzimidazole induces hypersensitivity from Fanconi anaemia cells lacking FANCD2.Figure optionsDownload full-size imageDownload as PowerPoint slide