Calothrixins, a new class of human DNA topoisomerase i poisons

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.