β-amino alcohols and their respective 2-phenyl-N-alkyl aziridines as potential DNA minor groove binders
作者:Miguel M. Vaidergorn、Zumira A. Carneiro、Carla D. Lopes、Sérgio de Albuquerque、Felipe C.C. Reis、Sofia Nikolaou、Juliana F.R. e Mello、Giovani L. Genesi、Gustavo H.G. Trossini、A. Ganesan、Flavio S. Emery
DOI:10.1016/j.ejmech.2018.07.055
日期:2018.9
It is known that aziridines and nitrogen mustards exert their biological activities, especially in chemotherapy, via DNA alkylation. The studied scaffold, 2-phenyl-1-aziridine, provides a distinct conformation compared to commonly used aziridines, and therefore, leads to a change in high-strained ring reactivity towards biological nucleophiles, such as DNA. The above series of compounds was tested
已知氮丙啶和氮芥通过DNA烷基化发挥其生物学活性,特别是在化学疗法中。与常用的氮丙啶相比,所研究的2-苯基-1-氮丙啶支架具有独特的构象,因此导致对生物亲核试剂(如DNA)的高应变环反应性发生变化。以上系列化合物已在三种乳腺癌细胞系中进行了测试:MCF-10,一种健康细胞;MCF-7,一种激素反应性癌细胞;MDA-MB-231是三阴性乳腺癌细胞。氮丙啶及其前体β-氨基醇均对这些细胞表现出活性,并且某些化合物的选择性指数高于用作对照的顺铂。在调查了细胞死亡的类型后,