Synthesis, biological evaluation, and molecular docking study of 3-(3′-heteroatom substituted-2′-hydroxy-1′-propyloxy) xanthone analogues as novel topoisomerase IIα catalytic inhibitor

Kyu Yeon Jun, Eun Young Lee, Mi Ja Jung, Ok Hee Lee, Eung Seok Lee, Hea Young Park Choo, Younghwa Na, Youngjoo Kwon

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Epoxide ring-opened xanthone derivatives were synthesized and tested for their topoisomerase inhibitory activity and cytotoxicity. Most of the compounds showed topo IIα specific inhibitory activity. To clarify the mechanism of action of these compounds, the most potent compound (compound 14) of the synthesized analogues was further studied by testing its ATPase inhibitory activity and through molecular docking experiments. The results showed that the topo IIα inhibitory activity of compound 14 was inversely proportional to ATP concentration. In the ATPase inhibitory test, ATP hydrolysis was reduced less efficiently by compound 14 (28.5 ± 4.6%) than novobiocin (60.4 ± 8.1%). Molecular docking study revealed compound 14 to have a stable binding pattern to the ATP-binding domain of human topo II.

Original languageEnglish
Pages (from-to)1964-1971
Number of pages8
JournalEuropean Journal of Medicinal Chemistry
Volume46
Issue number6
DOIs
StatePublished - Jun 2011

Keywords

  • ATP-competitive topoisomerase IIα inhibitor
  • Anti-cancer agents
  • Molecular docking
  • Xanthones

Fingerprint

Dive into the research topics of 'Synthesis, biological evaluation, and molecular docking study of 3-(3′-heteroatom substituted-2′-hydroxy-1′-propyloxy) xanthone analogues as novel topoisomerase IIα catalytic inhibitor'. Together they form a unique fingerprint.

Cite this