Synthesis and Ribonucleotide reductase inhibitory activity of thiosemicarbazones

Kesavan Krishnan, Kumari Prathiba, Venkatesan Jayaprakash, Arijit Basu, Nibha Mishra, Bingsen Zhou, Shuya Hu, Yun Yen

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Ribonucleotide reductase (RR) is an important therapeutic target for anticancer drugs. The structure of human RR features a 1:1 complex of two homodimeric subunits, hRRM1 and hRRM2. Prokaryotically expressed and highly purified recombinant human RR subunits, hRRM1 and hRRM2, were used for holoenzyme-based [3H]CDP reduction in vitro assay. Ten new thiosemicarbazones (7-16) were synthesized and screened for their RR inhibitory activity. Two thiosemicarbazones derived from p-hydroxy benzaldehyde (9 and 10) were found to be active but less potent than the standard, Hydroxyurea (HU). Guided by the activity of compounds 9 and 10, 11 new thiosemicarbazones (17-27) derived from p-hydroxy benzaldehyde were prepared and screened for their RR inhibitory activity. All the 11 compounds were more potent than HU.

Original languageEnglish
Pages (from-to)6248-6250
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number23
DOIs
Publication statusPublished - Dec 1 2008
Externally publishedYes

Keywords

  • [H]CDP reduction assay
  • hRRM1 and hRRM2
  • Human recombinant RR subunit
  • p-Hydroxybenzaldehyde thiosemicarbazones
  • RR inhibitory activity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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