Trifluoromethylated carboline compounds targeting DNA: Synthesis, binding and anti-proliferative effects on human cancer cell lines
作者:Sarita Sarkar、Olga I. Shmatova、Valentine G. Nenajdenko、Kakali Bhadra
DOI:10.1016/j.bioorg.2019.01.028
日期:2019.5
by beta-carboline compounds with amino alkyl chain and least with guanidine alkyl chain compounds. It decreased with increasing chain length. The bindings were entropically driven being more with guanidine alkyl chain analogs. Site preference and mode of binding with partial intercalation and external binding was supported by FTIR and viscosity. Cytotoxic potencies of the compounds were tested on seven
通过Pictet-Spengler环化反应制备了三套由咔啉衍生的化合物。这些四氢β-和γ-咔啉具有CF3基团,其具有可变长度的另外的氨基烷基链(α-或δ-位置)和胍烷基链(α-位置)。荧光,ITC,FTIR和粘度强调了这些分子与小牛胸腺DNA的结构活性关系。与DNA的结合导致荧光发射显着增强和猝灭。γ-咔啉类似物显示出最大的DNA结合,其次是具有氨基烷基链的β-咔啉化合物,而与胍基烷基链化合物的结合最少。它随着链长的增加而减少。结合被胍烷基链类似物更熵地驱动。通过FTIR和粘度来支持位点偏爱和具有部分插入和外部结合的结合模式。在七种不同的癌细胞系上测试了化合物的细胞毒性。与γ50位置相连的最小烷基链类似物Comp3,对HCT-116的细胞毒性最大,对HC50-116的GI50毒性最大,其次是胍烷基链化合物,但至β位置的氨基烷基链化合物显示出较差的细胞毒性。这些结果可能在设计新的咔啉衍生物作