respirantin and Leukemia-P388

By utilizing a bioassay-guided separation (P388 lymphocytic leukemia and a panel of human cancer cell lines) of fermentation broths from a Kitasatospora sp. collected from a tundra soil sample taken at the shore of the Beaufort Sea, we have isolated three powerful (GI50 to 0.0006 microg/mL) cancer cell growth inhibitors (1-3) and determined their structures to be closely related cyclodepsipeptides. From 380 L fermentations of Kitasatospora sp. were obtained 2.6 mg of a new cyclodepsipeptide designated kitastatin 1 (3), accompanied by the previously known respirantin (1, 10.8 mg) and its valeryl homologue (2, 4.8 mg). The structures were determined by employment of a series of high-resolution mass and 2D NMR spectroscopic analyses. The stereochemical assignments and overall structures were confirmed by subsequent total synthesis of depsipeptide 1, as reported in the accompanying contribution.

Topics: Actinobacteria; Animals; Antineoplastic Agents; Bacteria; Candida albicans; Depsipeptides; Drug Screening Assays, Antitumor; Humans; Leukemia P388; Mice; Microbial Sensitivity Tests; Molecular Structure