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

Karen Fahey; Liz O’Donovan; Miriam Carr; Michael P. Carty; Fawaz Aldabbagh

doi:10.1016/j.ejmech.2010.01.026

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

Karen Fahey
, Liz O’Donovan
, Miriam Carr
, Michael P. Carty
, Fawaz Aldabbagh

Institute for Health, Education & Society

National University of Ireland

Research output: Contribution to journal › Article › peer-review

Abstract

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

Original language	English
Pages (from-to)	1873-1879
Number of pages	7
Journal	European Journal of Medicinal Chemistry
Volume	45
Issue number	5
Early online date	20 Jan 2010
DOIs	https://doi.org/10.1016/j.ejmech.2010.01.026
Publication status	Published - May 2010

Keywords

Aziridine
Bioreductive
Cytotoxicity
Mitomycin C
Quinones

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

abstract = "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",

keywords = "Aziridine, Bioreductive, Cytotoxicity, Mitomycin C, Quinones",

author = "Karen Fahey and Liz O{\textquoteright}Donovan and Miriam Carr and Carty, \{Michael P.\} and Fawaz Aldabbagh",

year = "2010",

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doi = "10.1016/j.ejmech.2010.01.026",

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T1 - The influence of the aziridinyl substituent of benzimidazoles and benzimidazolequinones on toxicity towards normal and Fanconi anaemia cells

AU - Fahey, Karen

AU - O’Donovan, Liz

AU - Carr, Miriam

AU - Carty, Michael P.

AU - Aldabbagh, Fawaz

PY - 2010/5

Y1 - 2010/5

N2 - 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

AB - 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

KW - Aziridine

KW - Bioreductive

KW - Cytotoxicity

KW - Mitomycin C

KW - Quinones

U2 - 10.1016/j.ejmech.2010.01.026

DO - 10.1016/j.ejmech.2010.01.026

M3 - Article

SN - 0223-5234

VL - 45

SP - 1873

EP - 1879

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

IS - 5

ER -

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

Abstract

Keywords

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