Synthesis and biological research of novel azaacridine derivatives as potent DNA-binding ligands and topoisomerase II inhibitors.
Bioorg Med Chem
; 25(13): 3437-3446, 2017 07 01.
Article
em En
| MEDLINE
| ID: mdl-28511910
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Aza
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Acridinas
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DNA
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DNA Topoisomerases Tipo II
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Inibidores da Topoisomerase II
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Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article