In vitro and in silico assessment of DNA interaction, topoisomerase I and II inhibition properties of chrysosplenetin.

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 IC 50 value of 0.29 μM. 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 μM. 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. • Effects of chrysosplenetin on DNA and DNA topoisomerases were evaluated. • Chrysosplenetin did not cause damage to plasmid DNA. • Chrysosplenetin inhibited plasmid DNA damage induced by Fenton reagents. • Chrysosplenetin behaved as dual inhibitor of DNA topoisomerase I and II. • Binding mode, interactions with DNA and topoisomerases were predicted in silico. [ABSTRACT FROM AUTHOR]