Lemster Thomas, Pindur Ulf, Lenglet Gaelle, Depauw Sabine, Dassi Christelle, David-Cordonnier Marie-Hélène
Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Johannes Gutenberg-University, Mainz, Rheinland-Pfalz, Germany.
Eur J Med Chem. 2009 Aug;44(8):3235-52. doi: 10.1016/j.ejmech.2009.03.026. Epub 2009 Mar 27.
In the context of the design and synthesis of DNA ligands, some new hetarene annelated carbazoles were synthesized. As lead structure the intercalating tetracyclic systems pyrido[2,3-a]- and pyrido[4,3-a]-carbazoles and in one case a thieno[2,3-a]-carbazole were taken into account. A dialkyl amino amidic chain was introduced to the planar chromophoric system with the intent to generate minor groove binding properties. The cytotoxicity of some compounds 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 inhibition of DNA related functional enzymes of this new series of molecules.
在DNA配体的设计与合成背景下，合成了一些新型稠合杂芳烃咔唑。作为先导结构，考虑了具有嵌入作用的四环体系吡啶并[2,3-a]-和吡啶并[4,3-a]-咔唑，以及一例噻吩并[2,3-a]-咔唑。为了产生小沟结合特性，将二烷基氨基酰胺链引入平面发色体系。通过美国国立癌症研究所（NCI）的抗肿瘤筛选检测了一些化合物的细胞毒性。此外，还进行了生物物理和生化研究，以便获取有关该系列新分子的DNA结合特性以及对DNA相关功能酶抑制作用的一些信息。
