First synthesis of N-[(aziridin-2-yl)methyl]benzimidazolequinone and analysis of toxicity towards normal and Fanconi anemia cells.
A diazole is N-substituted with 1-trityl-2-methylaziridine and demethylated and oxidised with NBS under acidic conditions to give a benzimidazolequinone; this novel anti-tumour agent is marginally more cytotoxic than mitomycin C (MMC) towards the normal human fibroblast cell line GM00637, while the MMC-hypersensitive human Fanconi anaemia (FA) cell line, PD20i, lacking the FANCD2 protein, is also hypersensitive to the benzimidazolequinone, with expression of FANCD2 protein decreasing sensitivity to both MMC and the benzimidazolequinone.
O'Donovan
Liz
L
School of Chemistry, National University of Ireland, Galway, Ireland.
Carty
Michael P
MP
Aldabbagh
Fawaz
F
D001388:Aziridines / Q000138:chemical synthesis* / Q000633:toxicity*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005199:Fanconi Anemia / Q000473:pathology*; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000096:biosynthesis / Q000172:deficiency / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis* / Q000633:toxicity*; D012867:Skin / Q000166:cytology* / Q000187:drug effects*; D013237:Stereoisomerism; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D001388:Aziridines; D001562:Benzimidazoles; C499905:FANCD2 protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; C534258:N-((aziridin-2-yl)methyl)benzimidazolequinone; D011804:Quinolines; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue