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

Şöhretoğlu D. , Barut B., Sari S. , Özel A., Arroo R.

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, vol.163, pp.1053-1059, 2020 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 163
  • Publication Date: 2020
  • Doi Number: 10.1016/j.ijbiomac.2020.07.049
  • Page Numbers: pp.1053-1059


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 mu 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 mu 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. (C) 2020 Elsevier B.V. All rights reserved.