Atropisomeric 8-arylchromen-4-ones exhibit enantioselective inhibition of the DNA-dependent protein kinase (DNA-PK)

被引：13
|
作者：
Cano, Celine [1 ]
Golding, Bernard T. [1 ]
Haggerty, Karen [1 ]
Hardcastle, Ian R. [1 ]
Peacock, Marcus [2 ]
Griffin, Roger J. [1 ]
机构：
[1] Univ Newcastle, No Inst Canc Res, Sch Chem, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
[2] KuDOS Pharmaceut Ltd, Cambridge CB4 0PE, England
来源：
ORGANIC & BIOMOLECULAR CHEMISTRY | 2010年 / 8卷 / 08期
基金：
英国工程与自然科学研究理事会;
关键词：
DIRECTED ORTHO-METALATION; HUMAN TUMOR-CELLS; STRAND BREAK; POTENT; WORTMANNIN; RADIOSENSITIZATION; IDENTIFICATION; DISCOVERY; RADIATION; LY294002;
D O I：
10.1039/b926245h
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
Substitution at the 3-position of the dibenzothiophen-4-yl ring of 8-(dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-one NU7441, a potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor, with propyl, allyl or methyl enabled the separation by chiral HPLC of atropisomers. This is a consequence of restricted rotation about the dibenzothiophene-chromenone bond. Biological evaluation against DNA-PK of the pairs of atropisomers showed a marked difference in potency, with only one enantiomer being biologically active.
引用
收藏
页码：1922 / 1928
页数：7
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