Tian Zhi-yong, Xie Song-qiang, Du Yao-wu, Ma Yuan-fang, Zhao Jin, Gao Wen-yuan, Wang Chao-jie
Institute of Natural Products and Medicinal Chemistry, Henan University, Kaifeng 475001, China; Pharmacy College, Tianjin University, Tianjin 300072, China.
Eur J Med Chem. 2009 Jan;44(1):393-9. doi: 10.1016/j.ejmech.2008.02.044. Epub 2008 Mar 14.
Several naphthalimide polyamine conjugates were synthesized and evaluated for in vitro cytotoxicity against human leukemia K562, murine melanoma B16, Chinese hamster ovary CHO cell lines. Both triamine moieties and the length of spacers were crucial in elevating the potency of 1,8-naphthalimide. The typical compounds 5a and 5d exhibited excellent cell selectivity to cancer cells through the human hepatoma BEL-7402 and human normal hepatocyte QSG-7701 screens. In addition, 5d could disturb the cell cycle in B16 cells. The research on caspase activity and cytochrome c indicated that 5d could induce B16 cell apoptosis via both the mitochondrial and membrane death receptor pathways, and the Bcl-2 family numbers were involved in the control of apoptosis.
合成了几种萘二甲酰亚胺多胺缀合物，并评估了它们对人白血病K562、小鼠黑色素瘤B16、中国仓鼠卵巢CHO细胞系的体外细胞毒性。三胺部分和间隔基的长度对于提高1,8-萘二甲酰亚胺的效力至关重要。典型化合物5a和5d通过人肝癌BEL-7402和人正常肝细胞QSG-7701筛选，对癌细胞表现出优异的细胞选择性。此外，5d可干扰B16细胞的细胞周期。对半胱天冬酶活性和细胞色素c的研究表明，5d可通过线粒体和膜死亡受体途径诱导B16细胞凋亡，且Bcl-2家族成员参与了细胞凋亡的调控。
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