Purification and characterization of aseanostatins: Actinomycete-derived fatty acid inhibitors to myeloperoxidase release from human polymorphonuclear leukocytes

A. Ishida-Okawara, Y. Kimoto, K. Watanabe, K. Tokuda, M. Shibata, K. Masuda, Y. Takano, K. Kawaguchi, H. Akagawa, N. Nilubol, K. Hotta, K. Yazawa, Kazunaga Yazawa, K. Suzuki

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Abstract

We found inhibitors, designated aseanostatins P1 and P5, against myeloperoxidase (MPO) release from human polymorphonuclear leukocytes (PMN). Aseanostatins were extracted from an actinomycete isolated in Thailand and purified by a series of column chromatography of charcoal and silica gel, and HPLC. Physico-chemical characterization by gas liquid chromatography and GC-MS indicated that aseanostatins were fatty acids. The active forms of aseanostatins were recovered by hydrolyzing their methyl esters after HPLC. Two components P1 and P5 with the IC50 of 0.96 and 0.54 μg/ml to the MPO release were obtained as pure forms, indicating aseanostatin P5 was higher activity than aseanostatin P1. The component P1 was identical with 12-methyltridecanoic acid and P5 was indistinguishable to 12-methyltetradecanoic acid (ante-i-15:0). Aseanostatin P5 (1 μg/ml) did not inhibit β-glucuronidase release, but O2 - production a little. It has no effect on chemotaxis of PMN to fMet-Leu-Phe (10-8 M), PMN adhesion or phosphorylation of a 64-kD protein in the PMN cell-lysate system.

Original languageEnglish
Pages (from-to)524-532
Number of pages9
JournalJournal of Antibiotics
Volume44
Issue number5
Publication statusPublished - 1991
Externally publishedYes

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ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Ishida-Okawara, A., Kimoto, Y., Watanabe, K., Tokuda, K., Shibata, M., Masuda, K., Takano, Y., Kawaguchi, K., Akagawa, H., Nilubol, N., Hotta, K., Yazawa, K., Yazawa, K., & Suzuki, K. (1991). Purification and characterization of aseanostatins: Actinomycete-derived fatty acid inhibitors to myeloperoxidase release from human polymorphonuclear leukocytes. Journal of Antibiotics, 44(5), 524-532.