Nitrosoxacins A, B and C, new 5-lipoxygenase inhibitors.

The Journal of Antibiotics
1993.0

Abstract

In our continuing search for microbial metabolites that inhibit the activity of 5-lipoxygenase (5-LPO), we had reported carbazomycins1*, epocarbazolins2) as 5-LPO inhibitors. Further search resulted in the isolation of new 5-LPO inhibitors designated nitrosoxacins A, B and C from strain AA4091. In this paper, we describe the production, isolation and structural studies of these new inhibitors. The producing strain was isolated from a soil sample collected in Kisarazu City, Chiba Prefecture, Japan, and taxonomic studies indicated that the strain belonged to the genus Streptomyces. This strain was fermented in 500-ml Erlenmeyer flasks in 100 ml of medium (soluble starch 2.5%, glucose 1 %, Pharmamedia 1%, Brewer's yeast extract 0.3%, CaCO3 0.1% and Allophane 0.5%. The pH of the medium was adjusted to pH 7.0 before autoclaving.). The 5-LPO inhibitory activity was determined as described previously1}. The active substances were isolated according to the procedures shown in Scheme 1. Nitrosoxacins A, B and C complex were extracted from the fermentation broth with 1-butanol and each component was separated by reversed phase silica gel column chromatography followed by Sephadex LH-20 chromatography. They were obtained as white amorphous powders and were soluble in dimethyl sulfoxide and chloroform, slightly soluble in methanol and hexane, but insoluble in water.

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