Calothrixins, a new class of human DNA topoisomerase I poisons

J Nat Prod. 2009 Mar 27;72(3):438-42. doi: 10.1021/np8007232.

Abstract

Calothrixins A (1) and B (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 muM. The cell cycle effects of calothrixins 1-3 were also studied. Calothrixin B (2) produced G(1) arrest at 0.1 muM concentration, while higher concentrations of calothrixins 1 and 3 resulted in cell accumulation in both the S and G(2)/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.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Cycle / drug effects*
  • DNA Replication / drug effects
  • Drug Screening Assays, Antitumor
  • Humans
  • Indole Alkaloids / chemical synthesis
  • Indole Alkaloids / chemistry*
  • Indole Alkaloids / pharmacology*
  • Molecular Structure
  • Topoisomerase I Inhibitors*

Substances

  • Antineoplastic Agents
  • Indole Alkaloids
  • Topoisomerase I Inhibitors
  • calothrixin A
  • calothrixin B