Design, synthesis and biological evaluation of new oligopyrrole carboxamides linked with tricyclic DNA-intercalators as potential DNA ligands or topoisomerase inhibitors

被引:44
作者
David-Cordonnier, Marie-Helene
Hildebrand, Marie-Paule
Baldeyrou, Brigitte
Lansiaux, Amelie
Keuser, Christoph
Benzschawel, Kerstin
Lemster, Thomas
Pindur, Ulf
机构
[1] Univ Mainz, Inst Pharm, Dept Pharmaceut & Med Chem, D-55099 Mainz, Germany
[2] INSERM, U837 JPARC, Equipe 4, Inst Rech Canc Lille, F-59045 Lille, France
[3] Univ Lille 2, IMPRT, Inst Federat Rech 114, Lille, France
[4] Ctr Oscar Lambret, Lab Pharmacol Anitumorale, F-59020 Lille, France
关键词
DNA ligands; oligopyrrole carboxamides; hybrid molecules; DNA intercalation; DNA minor groove binding;
D O I
10.1016/j.ejmech.2006.12.039
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
In the context of the design and synthesis of minor groove binding and intercalating DNA ligands some new oligopyrrole carboxamides were synthesized. These hybrid molecules (combilexins) possess a variable and conformatively flexible spacer at the N-terminal end. As intercalating tricyclic systems acridone, acridine, anthraquinones and in a special case immostilbene terminate the N-terminal end of the pyrrole chain. The cytotoxicity was examined by the NCI antitumor screening, furthermore, biophysical as well as biochemical studies were performed in order to get some information about the DNA binding properties and topoisomerase inhibition effect of this new series of molecules. (c) 2007 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:752 / 771
页数:20
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