A study of the Topoisomerase II activity in HIV-1 replication using the ferrocene derivatives as probes

Anand K. Kondapi, Nathamu Satyanarayana, A. D. Saikrishna

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Human Topoisomerase II is present in two isoforms, 170 KDa α and 180 KDa β. Both the isoforms play a crucial role in maintenance of topological changes during DNA replication and recombination. It has been shown that Topoisomerase II activity is required for HIV-1 replication and the enzyme is phosphorylated during early time points of HIV-1 replication. In the present study, we have studied the molecular action of Topoisomerase II inhibitors, azalactone ferrocene (AzaFecp), Thiomorpholide amido methyl ferrocene (ThioFecp), and Ruthenium benzene amino pyridine (Ru(ben)Apy) on cell proliferation and also on various events of HIV-1 replication cycle. The Topoisomerase II β over-expressing neuroblastoma cell line shows a higher sensitivity to these compounds compared to the Sup-T1 cell line. All the three Topoisomerase II inhibitors show significant anti-HIV activity at nanomolar concentrations against an Indian isolate of HIV-193IN101 in Sup-T1 cell line. An analysis of action of these compounds on proviral DNA synthesis at 5 h of post-infection shows that they inhibit proviral DNA synthesis as well as the formation of pre-integration complexes completely. Further analysis, using polymerase chain reaction and western blot, showed that both the Topoisomerase II α and β isoforms are present in the pre-integration complexes, suggesting their significant role in HIV-1 replication.

Original languageEnglish (US)
Pages (from-to)123-132
Number of pages10
JournalArchives of Biochemistry and Biophysics
Volume450
Issue number2
DOIs
StatePublished - Jun 15 2006
Externally publishedYes

Keywords

  • Anti proliferation
  • Anti-HIV activity
  • Ferrocene derivatives
  • HIV infection
  • Organometallic compounds
  • Proviral DNA
  • Ruthenium derivatives
  • Topoisomerase II poisons
  • Topoisomerase II α
  • Topoisomerase II β

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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