DC 102, a new glycosidic pyrrolo(1,4)benzodiazepine antibiotic produced by Streptomyces sp.

The Journal of Antibiotics
1988.0

Abstract

We screened microorganisms isolated from soil and plants for their ability to produce antitumor antibiotics and isolated a new glycosidic pyrrolo(1,4)benzodiazepine antibiotic named DC102 from a cultured broth of a Streptomycete. This communication reports the production, isolation and characterization of DC102. The producing organism was isolated from soil collected in Onuma Park, Hokkaido, Japan. Fermentation was carried out using specific seed and production media, with conditions including 28°C incubation, 300 rpm stirring, and 18 liters/minute aeration. Isolation and purification involved sequential use of Diaion HP-20, Diaion SK-104 (NH4+ form), silica gel, and DEAE-Sepharose CL-6B (Cl- form) columns, yielding 5 mg of DC102. DC102 is a basic white powder with a melting point of 120°C (dec), solubility in methanol and ethanol (readily), water and acetone (slightly), and insolubility in chloroform and n-hexane. It has UV absorption maxima at 210, 244 (sh), and 310 nm, an EI-mass m/z of 429.2261 (M+ - CH3OH, calcd for C23H31N3O5: 429.2242), and specific IR and 13C NMR spectra. A positive reaction to β-anisidine indicated a sugar moiety, and its structure (assigned via NMR) differs from sibiromycin. DC102 exhibited weak antimicrobial activity against Gram-positive bacteria (e.g., Streptococcus faecium, Bacillus subtilis) and significant antitumor activity against murine leukemia P388, with a 54% increase in life span at a dose of 0.5 mg/kg. The LD50 value was 1.5 mg/kg (intraperitoneal) in mice.

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