Abstract: Siwenmycin, a novel anthracycline antibiotic, was first isolated from a culture of streptomyces galilaeus var. siwenesis of a piece of chinese Siwenmycin inhibited purified mammalian DNA topoisomerase II with a maximal inhibitory concentration of 25 μmol/L as assessed by the ATP-dependent relaxation of supercoiled pBR322 DNA. DNA cleavage aI1d relaxing reactions induced by DNA topoisomerase II obtained from Bel 7402 cells treated with siwenmycin, were increased by 5-fold comparing with control. In addition, siwenmycin also inhibited the catalytic activity of DNA topoisomerases I and induced single-strand DNA breakage in vitro. The results showed that topoisomerases I and II are the cellular targets of siwenmycin, the study of these targets will provide a rational basis for the structural design of aclacinomycin analogues.

Key words: Anthracycline antibiotics, Siwenmycin, DNA topoisomerases, Tumor targets