K97-0239A and B, new inhibitors of macrophage foam cell formation, produced by Streptomyces sp. K97-0239

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  • NAMATAME Ichiji
    Kitasato Institute for Life Sciences, Kitasato University Japan Science and Technology Corporation
  • TOMODA Hiroshi
    Kitasato Institute for Life Sciences, Kitasato University
  • MATSUDA Daisuke
    Faculty of Pharmaceutical Sciences, Tokyo University of Science
  • TABATA Noriko
    Kitasato Institute for Life Sciences, Kitasato University
  • KOBAYASHI Susumu
    Faculty of Pharmaceutical Sciences, Tokyo University of Science
  • OMURA Satoshi
    Kitasato Institute for Life Sciences, Kitasato University

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  • K97-0239A and B, new inhibitors of macrophage foam cell formation, produced by <i>Streptomyces</i> sp. K97-0239

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Streptomyces sp. K97-0239, a soil isolate, was found to produce inhibitors of lipid droplet formation in mouse peritoneal macrophages. Two compounds, K97-0239A and B, were isolated from the culture broth of the producing strain, and their structures were elucidated by spectroscopic analyses including various NMR experiments. They were cyclic lipopeptides comprising 2, 3-diaminopropionic acid, 4-(aminomethyl)-2, 2-dimethyl-5-oxo-1-imidazolidineacetic acid and phenylalanine/leucine as ring units, and 3-(13-hydroxytetradeca-2, 4-dienoylamino)-acrylic acid as lipophilic side chains. They caused a dose-dependent reduction in the number and size of cytosolic lipid droplets in macrophages at least up to 15μM without any cytotoxic effect on macrophages. [14C] Cholesteryl ester synthesis from [14C] oleic acid by macrophages was inhibited by K97-0239s with IC50 values of 1.5-1.7μM.

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