Synthesis and Biological Evaluation of <i>N</i>-(Anthracen-9-ylmethyl)triamines as Molecular Recognition Elements for the Polyamine Transporter
作者:Chaojie Wang、Jean-Guy Delcros、John Biggerstaff、Phanstiel
DOI:10.1021/jm030028w
日期:2003.6.1
An efficient modular synthesis of N(1)-substituted triamines containing different tether lengths between nitrogen centers was developed. A series of N(1)-(9-anthracenylmethyl)triamines were evaluated for biological activity in L1210 (murine leukemia), alpha-difluoromethylornithine (DFMO)-treated L1210, Chinese hamster ovary (CHO), and CHO-MG cell lines. All triamines 8 had increased potency in DFMO-treated
开发了N(1)取代的三胺在氮中心之间包含不同系链长度的有效模块化合成。评估了一系列N(1)-(9-蒽基甲基)三胺在L1210(鼠白血病),α-二氟甲基鸟氨酸(DFMO)处理的L1210,中国仓鼠卵巢(CHO)和CHO-MG细胞系中的生物活性。所有三胺8在DFMO处理的L1210细胞中均具有增强的效力。4,4-和5,4-三胺系统对多胺转运蛋白(PAT)的亲和力最高,L1210 K(i)值分别为1.8和1.7 microM。这种趋势也反映在CHO研究中。令人惊讶的是,各自的4,4-和5,4-三胺系统在含有活性多胺转运蛋白的CHO细胞中具有150倍和38倍的细胞毒性。最初的显微镜研究显示,在用N(1)-(9-蒽基甲基)高嘧啶(4,4-三胺)偶联物处理过的A375黑色素瘤细胞中,水泡结构快速形成。总之,已鉴定出4,4-和5,4-三胺是选择性的载体基序,可通过PAT将蒽导入细胞。