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

Date

2020-07-13

Advisors

Journal Title

Journal ISSN

ISSN

0141-8130

Volume Title

Publisher

Elsevier

Type

Article

Peer reviewed

Yes

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.

Description

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.

Keywords

Chrysosplenetin, DNA, Topoisomerase, Polymethoxyflavones

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

Rights

Research Institute

Leicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)