Calothrixins, a new class of human DNA topoisomerase i poisons

Qasim A. Khan, Jun Lu, Sidney Hecht

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Calothrixins A (1)andB(2) were converted to their O- and N-methylated derivatives, respectively. All four compounds were found to act as poisons of DNA topoisomerase I and to do so reversibly. Three of the calothrixins (1-3) were tested for their cytotoxicity toward cultured (p53 proficient) CEM leukemia cells and found to exhibit IC 50 values ranging from 0.20 to 5.13 μM. The cell cycle effects of calothrixins 1-3 were also studied. Calothrixin B (2) produced G 1 arrest at 0.1 μM concentration, while higher concentrations of calothrixins 1 and 3 resulted in cell accumulation in both the S and G2/M phases of the cell cycle. The cell cycle effects produced by the calothrixins were more readily reversible upon removal of the compounds than those produced by camptothecin.

Original languageEnglish (US)
Pages (from-to)438-442
Number of pages5
JournalJournal of Natural Products
Volume72
Issue number3
DOIs
StatePublished - Mar 27 2009

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ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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