带有氨基烷基侧链的新型甲基硫代萘二甲酰亚胺的合成、抗肿瘤评估及DNA光裂解活性

Synthesis, antitumor evaluation and DNA photocleaving activity of novel methylthiazonaphthalimides with aminoalkyl side chains.

作者信息

Li Zhigang, Yang Qing, Qian Xuhong

机构信息

State Key Lab. of Fine Chemicals, Dalian University of Technology, PO Box 158, Zhongshan Road, Dalian 116012, China.

出版信息

Bioorg Med Chem Lett. 2005 Jun 15;15(12):3143-6. doi: 10.1016/j.bmcl.2005.04.012.

DOI:10.1016/j.bmcl.2005.04.012

PMID:15876532

Abstract

A series of methylthiazonaphthalimides was synthesized and quantitatively evaluated as efficient DNA intercalators, antitumor agents and DNA photocleavers. A(1) showed both efficient antitumor activities against cell lines of A549 and P388 with IC50 of 82.8 and 31 nM, respectively. A(3) was the strongest antitumor agent against A549 with the IC50 of 20.8 nM. A(2), the most efficient DNA intercalator, was found to be the strongest DNA photocleaver via superoxide anion. An explanation was given for the disaccord between antitumor and DNA photocleaving activities.

摘要

合成了一系列甲基硫代萘二甲酰亚胺，并对其作为有效的DNA嵌入剂、抗肿瘤剂和DNA光裂解剂进行了定量评估。A(1)对A549和P388细胞系均显示出有效的抗肿瘤活性，IC50分别为82.8和31 nM。A(3)是对A549最强的抗肿瘤剂，IC50为20.8 nM。A(2)是最有效的DNA嵌入剂，通过超氧阴离子被发现是最强的DNA光裂解剂。对其抗肿瘤活性和DNA光裂解活性之间的不一致给出了解释。