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

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

  • Int J Biol Macromol. 2020 Nov 15:163:1053-1059. doi: 10.1016/j.ijbiomac.2020.07.049.
Didem Şöhretoğlu 1,  Burak Barut 2,  Suat Sari 3,  Arzu Özel 4,  Randolph Arroo 5
Affiliations

Affiliations

  • 1 Hacettepe University, Faculty of Pharmacy, Department of Pharmacognosy, Sıhhiye, Ankara, TR-06100 Ankara, Turkey. Electronic address: [email protected].
  • 2 Karadeniz Technical University, Faculty of Pharmacy, Department of Biochemistry, Trabzon, Turkey.
  • 3 Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Sıhhiye, Ankara, TR-06100 Ankara, Turkey.
  • 4 Karadeniz Technical University, Faculty of Pharmacy, Department of Biochemistry, Trabzon, Turkey; Karadeniz Technical University, Drug and Pharmaceutical Technology Application and Research Center, Trabzon, Turkey.
  • 5 De Montfort University, Leicester School of Pharmacy, The Gateway, Leicester LE1 9BH, United Kingdom.
PMID: 32673727 DOI: 10.1016/j.ijbiomac.2020.07.049
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 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.

Keywords

Chrysosplenetin; DNA; Flavonoid; Flavonol; Topoisomerase.

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