In vitro and in silico assessment of DNA interaction, topoisomerase I and II inhibition properties of chrysosplenetin.
Int J Biol Macromol
; 163: 1053-1059, 2020 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-32673727
ABSTRACT
Chrysosplenetin is a methoxyflavone with reported anti-cancer effect. We tested its cytotoxic effect on the MCF-7 breast cancer cell line, and determined its effect on DNA intercalation and on the activity of topoisomerases I and II. The compound inhibited proliferation MCF-7 with an IC50 value of 0.29⯵M. Chrysosplenetin did not initiate plasmid DNA cleavage but, in a concentration-dependent manner, protected plasmid DNA against damage induced by Fenton reagents. Furthermore, it possessed dual Topoisomerase I and II inhibitory properties. Especially, it inhibited topoisomerase II by 83-96% between the range 12.5-100⯵M. In the light of these experimental findings, molecular docking studies were performed to understand binding mode, interactions and affinity of chrysosplenetin with DNA, and with topoisomerases I and II. These studies showed that of 4-chromone core and the hydroxyl and methoxy groups important for both intercalation with DNA and topoisomerase I and II inhibition.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Flavonoides
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DNA
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DNA Topoisomerases Tipo II
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DNA Topoisomerases Tipo I
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Inibidores da Topoisomerase I
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Inibidores da Topoisomerase II
Limite:
Humans
Idioma:
En
Revista:
Int J Biol Macromol
Ano de publicação:
2020
Tipo de documento:
Article