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A novel inhibitor of topoisomerases designated as topostatin was isolated from the culture filtrate of Thermomonospora alba strain No. 1520. Topostatin inhibited the relaxation of supercoiled pBR322 DNA by calf thymus topoisomerase I, and also inhibited the relaxation of supercoiled pBR322 DNA and decatenation of kinetoplast DNA by human placenta topoisomerase II. Topostatin had neither ability to stabilize the cleavable complex nor ability to intercalate into DNA strands. The inhibitor exhibited growth inhibitory activity against the tumor cells (SNB-75 and SNB-78) of central nervous system, but did not exhibit any antimicrobial activity against Gram-positive and Gram-negative bacteria, yeasts and fungi.

journal of antibiotics

Topostatin, a Novel Inhibitor of Topoisomerases I and II Produced by Thermomonospora alba Strain No. 1520. I. Taxonomy, Fermentation, Isolation and Biological Activities.