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.
Fahey
Karen
K
School of Chemistry, National University of Ireland, Galway, Ireland.
O'Donovan
Liz
L
Carr
Miriam
M
Carty
Michael P
MP
Aldabbagh
Fawaz
F
D001388:Aziridines / Q000737:chemistry*; D001562:Benzimidazoles / Q000737:chemistry / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005199:Fanconi Anemia / Q000473:pathology*; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D011809:Quinones / Q000737:chemistry / Q000633:toxicity*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001388:Aziridines; D001562:Benzimidazoles; D011809:Quinones