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 IC50 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.
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Citation : Şöhretoğlu, D., Barut, B., Sari, S., Özel, A., Arroo, R. (2020) In vitro and in silico assessment of DNA interaction, topoisomerase I and II inhibition properties of chrysosplenetin. International Journal of Biological Macromolecules, 163, pp. 1053-1059
ISSN : 0141-8130
Research Institute : Leicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)
Peer Reviewed : Yes
- Leicester School of Pharmacy