K1115 A, a New Anthraquinone that Inhibits the Binding of Activator Protein-1(AP-1) to its Recognition Sites. II. Taxonomy, Fermentation, Isolation, Physico-chemical Properties and Structure Determination.

A new inhibitor of the action of activator protein-1 (AP-1), designated K1115 A, was isolated from the fermentation broth of an actinomycete strain Mer-K1115.K1115 A was determined to be a new anthraquinone, 3,8-dihydroxy-1-propylanthraquinone-2-carboxylic acid, based on spectroscopic analysis, derivatization experiments and biosynthetic studies with 13C-enriched acetic acid.Two co-produced compounds, K1115 B1 and B2, were also isolated and characterized as new members of the naphthopyranomycin and exfoliamycin group.In the course of our screening studies to find novel anti-inflammatory agents, an actinomycete strain Mer-K1115 was discovered to produce a new anthraquinone, named K1115 A (1). Compound 1 showed selective inhibitory activity against the direct binding of activator protein-1 (AP-1) to AP-1 oligonucleotide in gel retardation assay, and had an anti-inflammatory effect in the phorbol myristate acetate-induced ornithine decarboxylase activation model in mice1).The producing strain was identified as Streptomyces griseorubiginosus by means of taxonomical studies.Compound 1 is an acidic substance, which was recovered from the fermentation broth by 1-butanol extraction and effectively purified by chromatography with assay-guided fractionation.Its