Journal
JOURNAL OF NATURAL PRODUCTS
Volume 72, Issue 3, Pages 438-442Publisher
AMER CHEMICAL SOC
DOI: 10.1021/np8007232
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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 IC50 values ranging from 0.20 to 5.13 mu M. The cell cycle effects of calothrixins 1-3 were also studied. Calothrixin B (2) produced G(1) arrest at 0.1 mu M 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.
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