Synthesis and toxicity towards normal and cancer cell lines of benzimidazolequinones containing fused aromatic rings and 2-aromatic ring substituents

Eoin M. Moriarty; Miriam Carr; Sarah Bonham; Michael P. Carty; Fawaz Aldabbagh

doi:10.1016/j.ejmech.2010.05.025

Synthesis and toxicity towards normal and cancer cell lines of benzimidazolequinones containing fused aromatic rings and 2-aromatic ring substituents

Eoin M. Moriarty
, Miriam Carr
, Sarah Bonham
, Michael P. Carty
, Fawaz Aldabbagh

National University of Ireland

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

Abstract

A facile 6-exo-trig cyclization of σ-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 μM. 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.

Original language	English
Pages (from-to)	3762-3769
Number of pages	8
Journal	European Journal of Medicinal Chemistry
Volume	45
Issue number	9
Early online date	19 May 2010
DOIs	https://doi.org/10.1016/j.ejmech.2010.05.025
Publication status	Published - Sept 2010
Externally published	Yes

Keywords

Bioreductive
Heterocyclic compounds
NQO1
Quinones

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title = "Synthesis and toxicity towards normal and cancer cell lines of benzimidazolequinones containing fused aromatic rings and 2-aromatic ring substituents",

abstract = "A facile 6-exo-trig cyclization of σ-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 μM. 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.",

keywords = "Bioreductive, Heterocyclic compounds, NQO1, Quinones",

author = "Moriarty, \{Eoin M.\} and Miriam Carr and Sarah Bonham and Carty, \{Michael P.\} and Fawaz Aldabbagh",

year = "2010",

month = sep,

doi = "10.1016/j.ejmech.2010.05.025",

language = "English",

volume = "45",

pages = "3762--3769",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson s.r.l.",

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}

TY - JOUR

T1 - Synthesis and toxicity towards normal and cancer cell lines of benzimidazolequinones containing fused aromatic rings and 2-aromatic ring substituents

AU - Moriarty, Eoin M.

AU - Carr, Miriam

AU - Bonham, Sarah

AU - Carty, Michael P.

AU - Aldabbagh, Fawaz

PY - 2010/9

Y1 - 2010/9

N2 - A facile 6-exo-trig cyclization of σ-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 μM. 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.

AB - A facile 6-exo-trig cyclization of σ-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 μM. 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.

KW - Bioreductive

KW - Heterocyclic compounds

KW - NQO1

KW - Quinones

U2 - 10.1016/j.ejmech.2010.05.025

DO - 10.1016/j.ejmech.2010.05.025

M3 - Article

SN - 0223-5234

VL - 45

SP - 3762

EP - 3769

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

IS - 9

ER -

Synthesis and toxicity towards normal and cancer cell lines of benzimidazolequinones containing fused aromatic rings and 2-aromatic ring substituents

Abstract

Keywords

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