TAN-1120, A NEW ANTHRACYCLINE WITH POTENT ANGIOSTATIC ACTIVITY

A potent angiogenesis-inhibitory compound TAN-1120 was found to be pro duced by a Streptomyces species isolated from a soil sample. The produ cing organism was characterized as a new subspecies of S. triangulatus and named S. triangulatus subsp. angiostaticus subsp. nov. due to its specific ability to produce the compound. This substance was isolated as a red powder by a combination of organic solvent extraction, silic a gel column chromatography and preparative HPLC using an ODS column. Its structure was elucidated by chemical reactions and spectral analys es to be a new baumycin-group anthracycline. Reduction of TAN-1120 gav e two compounds, a deoxy derivative and baumycin A1. TAN-1120 showed r emarkably potent angiostatic activity in two conventional angiogenesis assay systems in vivo, while doxorubicin and daunomycin had far weake r activity. It strongly inhibited proliferation of vascular endothelia l cells but did not prevent capillary cord formation in vitro by the e ndothelial cells on extracellular matrix-coated plates. TAN-1120 is on e of the most potent angiostatic agents reported.