School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China.
Eur J Med Chem. 2010 Nov;45(11):4740-5. doi: 10.1016/j.ejmech.2010.07.037. Epub 2010 Jul 24.
In a continuing effort to develop novel β-carbolines endowed with better pharmacological profile, a series of water-soluble β-carbolines bearing a flexible amino side chain was designed and synthesized, and the cytotoxic activities in vitro of these compounds were evaluated. The N(9)-arylated alkyl substituted β-carbolines represented the most interesting cytotoxic agents, and compounds 4c and 4d were found to be the most potent compounds with IC(50) values lower than 10 μM against ten human tumor cell lines. The results confirmed that the N(9)-arylated alkyl substituents of β-carboline played a very important role in the modulation of the cytotoxic potencies. In addition, the interaction with DNA of these compounds was also investigated, these compounds were found to exhibit significant DNA binding affinity.
为了开发具有更好药理学特性的新型β-咔啉类化合物，我们设计并合成了一系列带有柔性氨基侧链的水溶性β-咔啉类化合物，并对这些化合物的体外细胞毒性进行了评估。N(9)-芳基取代的烷基取代β-咔啉类化合物代表了最有前途的细胞毒性药物，其中化合物 4c 和 4d 的活性最强，对十种人肿瘤细胞系的 IC50 值均低于 10 μM。结果证实，β-咔啉的 N(9)-芳基取代烷基在调节细胞毒性方面发挥了非常重要的作用。此外，还研究了这些化合物与 DNA 的相互作用，发现它们具有显著的 DNA 结合亲和力。
