分化诱导剂的合成及晶体结构

Synthesis and Crystal Structures of Cancer Cell Differentiation Inducers

合成出四个分化诱导剂,N,N,N＇-四乙酰己二胺(I),1,6一烟酰己二胺(Ⅱ),1,6-二(3,5-二氧哌嗪)己烷(Ⅲ)和1,6-二[3,3'-(5,5-二甲基乙内酰脲)]己烷(Ⅳ),对合成方一法和路线进行了优化,并通过元素分析、质谱、核磁和红外进行了表征,测定了化合物Ⅲ对入白血病细胞的分化诱导活性,利用单晶X射线四圆衍射测定了化合物Ⅳ的晶体结构,并与化合物I,Ⅱ,Ⅲ的晶体结构进行了比较.

Four effective differentiation inducers, the derivatives of HMBA, N, N, N', N' - tetracetylhexamethylenediamine, N, N' - hexamethylenebis (3 - pyridinecarboxamide), 4, 4' - (hexane - 1, 6 - diyl)bis(piperazine - 2, 6 - dione) and 3, 3' - (hexane - 1, 6 - diyl) bis (5, 5 - dimethylhydantoin), have been synthesized and identified by MS, NMR, IR and elemental analysis. The synthetic methods and routes have been optimized. The anticancer activity of 4, 4' - (hexane - 1, 6 - diyl) bis (piperazine - 2, 6 dione) against human erythroleukemia K562 cells was tested and its potency is ten times greater than ICRF 154[4, 4' - (ethane - 1, 2 - diyl) bis ( piperazine - 2, 6 - dione) I. The structure of compound IV was determined by single crystal X - ray diffraction and compared with compounds I, II, III. In the structures of these compounds, the hexamethylene chain is fully extended, which can increase the flexibility of the molecule. There are hydrogen bonds in compounds II, M, IV. It is found that the hydrogen bonds and the ring structure of the functional groups can influence the activity of the compounds.