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

27 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

Fingerprint

Thiosemicarbazones
Ribonucleotide Reductases
Hydroxyurea
Cytidine Diphosphate
Holoenzymes
Assays
Pharmaceutical Preparations

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

Cite this

Synthesis and Ribonucleotide reductase inhibitory activity of thiosemicarbazones. / Krishnan, Kesavan; Prathiba, Kumari; Jayaprakash, Venkatesan; Basu, Arijit; Mishra, Nibha; Zhou, Bingsen; Hu, Shuya; Yen, Yun.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 18, No. 23, 01.12.2008, p. 6248-6250.

Research output: Contribution to journalArticle

Krishnan, K, Prathiba, K, Jayaprakash, V, Basu, A, Mishra, N, Zhou, B, Hu, S & Yen, Y 2008, 'Synthesis and Ribonucleotide reductase inhibitory activity of thiosemicarbazones', Bioorganic and Medicinal Chemistry Letters, vol. 18, no. 23, pp. 6248-6250. https://doi.org/10.1016/j.bmcl.2008.09.097
Krishnan, Kesavan ; Prathiba, Kumari ; Jayaprakash, Venkatesan ; Basu, Arijit ; Mishra, Nibha ; Zhou, Bingsen ; Hu, Shuya ; Yen, Yun. / Synthesis and Ribonucleotide reductase inhibitory activity of thiosemicarbazones. In: Bioorganic and Medicinal Chemistry Letters. 2008 ; Vol. 18, No. 23. pp. 6248-6250.
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