Yuan Z M, Rosen D M, Egorin M J, Callery P S
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore 21201.
Biochem Pharmacol. 1994 Apr 29;47(9):1587-92. doi: 10.1016/0006-2952(94)90536-3.
Two isomeric aziridine-containing analogs of spermidine, a polyamine, were synthesized and evaluated for cytotoxic activity against cancer cell lines. Replacement of one of the primary amino groups of spermidine with an aziridinyl functionality yielded either N1-aziridinylspermidine [N-(3-aziridinylpropyl)-1,4-diaminobutane] or N8-aziridinylspermidine [N-(4-aziridinylbutyl)-1,3-diaminopropane]. N1-Aziridinylspermidine was cytotoxic in vitro against L1210 murine leukemia cells (IC50 0.15 microM) and HL60 human leukemia cells (IC50 0.11 microM). N8-Aziridinylspermidine was slightly less potent against L1210 (IC50 0.31 microM) and HL60 (IC50 0.30 microM) cells. When screened by the Developmental Therapeutics Program of the National Cancer Institute, these compounds proved cytotoxic against a wide variety of tumor types. Both compounds inhibited incorporation of radiolabeled thymidine, uridine, and valine into tricholoracetic acid-precipitable material by L1210 cells. Aminoguanidine did not affect the potency of the aziridinylspermidines.
合成了多胺亚精胺的两种含氮丙啶的同分异构体类似物，并评估了它们对癌细胞系的细胞毒性活性。用氮丙啶基官能团取代亚精胺的一个伯氨基，得到N1-氮丙啶基亚精胺[N-(3-氮丙啶基丙基)-1,4-二氨基丁烷]或N8-氮丙啶基亚精胺[N-(4-氮丙啶基丁基)-1,3-二氨基丙烷]。N1-氮丙啶基亚精胺在体外对L1210小鼠白血病细胞（IC50为0.15微摩尔）和HL60人白血病细胞（IC50为0.11微摩尔）具有细胞毒性。N8-氮丙啶基亚精胺对L1210（IC50为0.31微摩尔）和HL60（IC50为0.30微摩尔）细胞的效力略低。当通过美国国立癌症研究所的发育治疗项目进行筛选时，这些化合物对多种肿瘤类型均显示出细胞毒性。两种化合物均抑制L1210细胞将放射性标记的胸苷、尿苷和缬氨酸掺入三氯乙酸可沉淀物质中。氨基胍不影响氮丙啶基亚精胺的效力。
