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Synthesis and biological research of novel azaacridine derivatives as potent DNA-binding ligands and topoisomerase II inhibitors.

Abstract：

:DNA and DNA-related enzymes are one of the most effective and common used intracellular anticancer targets in clinic and laboratory studies, however, most of DNA-targeting drugs suffered from toxic side effects. Development of new molecules with good antitumor activity and low side effects is important. Based on computer aided design and our previous studies, a series of novel azaacridine derivatives were synthesized as DNA and topoisomerases binding agents, among which compound 9 displayed the best antiproliferative activity with an IC50 value of 0.57μM against U937 cells, which was slightly better than m-AMSA. In addition, compound 9 displayed low cytotoxicity against human normal liver cells (QSG-7701), the IC50 of which was more than 3 times lower than m-AMSA. Later study indicated that all the compounds displayed topoisomerases II inhibition activity at 50μM. The representative compound 9 could bind with DNA and induce U937 apoptosis through the exogenous pathway.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Li D,Yuan Z,Chen S,Zhang C,Song L,Gao C,Chen Y,Tan C,Jiang Y

doi

10.1016/j.bmc.2017.04.030

subject

Has Abstract

pub_date

2017-07-01 00:00:00

pages

3437-3446

issue

13

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(17)30053-6

journal_volume

25

pub_type

杂志文章

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