Bergeron R J, Hawthorne T R, Vinson J R, Beck D E, Ingeno M J
Department of Medicinal Chemistry, College of Pharmacy University of Florida, Gainesville 32610.
Cancer Res. 1989 Jun 1;49(11):2959-64.
The impact of the polyamine analogues, N1,N11-diethylnorspermine (DENSPM), N1,N12-diethylspermine (DESPM), and N1,N14-diethylhomospermine (DEHSPM) on the growth properties of L1210 murine leukemia cells is compared. The order of antiproliferative activity of the three compounds is shown to be DEHSPM greater than DESPM greater than DENSPM with average 96-h IC50 values of 0.06, 0.18, and 1.3 microM, respectively. Trypan blue exclusion suggests that the cytotoxic behavior of the compounds is not apparent until 96 h after exposure to the analogues. DEHSPM is shown to act more quickly and demonstrates the most profound cytotoxic effects at 144 h. Competitive uptake studies with spermidine reveal DESPM and DEHSPM to have essentially identical Ki values of 1.4 and 1.6 microM, respectively, while DENSPM indicates a substantially higher Ki value of 17 microM. Finally, although the analogues reduce the levels of putrescine, spermidine, and spermine in L1210 cells, if the concentration of polyamines in the cell, including analogues, is expressed on a nitrogen equivalence basis, the total cationic charge with which the polyamines are associated is conserved.
比较了多胺类似物N1,N11 - 二乙基亚精胺（DENSPM）、N1,N12 - 二乙基亚精胺（DESPM）和N1,N14 - 二乙基高亚精胺（DEHSPM）对L1210小鼠白血病细胞生长特性的影响。结果显示，这三种化合物的抗增殖活性顺序为DEHSPM大于DESPM大于DENSPM，其平均96小时IC50值分别为0.06、0.18和1.3微摩尔。台盼蓝排斥试验表明，直到接触类似物96小时后，这些化合物的细胞毒性行为才明显显现。结果表明，DEHSPM作用更快，在144小时时表现出最显著的细胞毒性作用。用亚精胺进行的竞争性摄取研究表明，DESPM和DEHSPM的Ki值基本相同，分别为1.4和1.6微摩尔，而DENSPM的Ki值则显著更高，为17微摩尔。最后，尽管这些类似物降低了L1210细胞中腐胺、亚精胺和精胺的水平，但如果细胞中的多胺浓度（包括类似物）以氮当量为基础表示，则与多胺相关的总阳离子电荷是守恒的。
