PURIFICATION AND CHARACTERIZATION OF ASEANOSTATINS: ACTINOMYCETE-DERIVED FATTY ACID INHIBITORS TO MYELOPEROXIDASE RELEASE FROM HUMAN POLYMORPHONUCLEAR LEUKOCYTES

We found inhibitors, designated aseanostatins PI 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....

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Published in:Journal of antibiotics 1991/05/25, Vol.44(5), pp.524-532
Main Authors: ISHIDA-OKAWARA, AKIKO, KIMOTO, YUKIO, WATANABE, KAZUO, TOKUDA, KOICHI, SHIBATA, MICHIO, MASUDA, KAORI, TAKANO, YUKIE, KAWAGUCHI, KAZUE, AKAGAWA, HISAYOSHI, NILUBOL, NALINE, HOTTA, KUNIMOTO, YAZAWA, KAZUNAGA, MIZUNO, SATOSHI, SUZUKI, KAZUO
Format: Article
Language:English
Subjects:
Actinomycetaceae
Actinomycetales - isolation & purification
Actinomycetales - metabolism
Anti-Bacterial Agents - isolation & purification
Anti-Bacterial Agents - pharmacology
Biological and medical sciences
Fatty Acids - antagonists & inhibitors
Fatty Acids - isolation & purification
Fatty Acids - pharmacology
Humans
Immunomodulators
Medical sciences
Neutrophils - drug effects
Neutrophils - metabolism
Peroxidase - blood
Peroxidase - metabolism
Pharmacology. Drug treatments
Superoxides - metabolism
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Summary:We found inhibitors, designated aseanostatins PI 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 PI and P5 with the IC50 of 0.96 and 0.54μg/ml to the MPO release were obtained as pure forms, indicating aseanostatin P5 was higher activity than aseanostatin PI. The component PI was identical with 12-methyltridecanoic acid and P5 was indistinguishable to 12-methyltetradecanoic acid (ante-i-15:0). Aseanostatin P5 (1μg/ml) did not inhibit β-glucuronidase release, but O2- production a little. It has no effect on chemotaxis of PMN to fMet-Leu-Phe (10-8M), PMN adhesion or phosphorylation of a 64-kD protein in the PMN cell-lysate system.
ISSN:0021-8820
1881-1469
DOI:10.7164/antibiotics.44.524