A NEW TOPOISOMERASE-II INHIBITOR, BE-10988, PRODUCED BY A STREPTOMYCETE .1. TAXONOMY, FERMENTATION, ISOLATION AND CHARACTERIZATION

A new topoisomerase inhibitor, BE-10988, was isolated from the culture broth of a strain of actinomycetes. The producing strain had a close resemblance to Streptomyces fimicarius and Streptomyces xanthocidicus. The active principle was extracted from the whole broth of strain BA10988 with ethyl acetate and purified by silica gel chromatography and by HPLC. BE-10988 increased DNA-topoisomerase complex formation and inhibited the growth of both doxorubicin-resistant and vincristine-resistant P388 murine leukemia cell lines, as well as sensitive P388 cell lines.