Thrazarine, a new antitumor antibiotic. I. Taxonomy, fermentation, isolation and biological properties

• Published in: Journal of antibiotics Vol. 41; no. 11; p. 1561
• Main Authors: Kameyama, T, Takahashi, A, Matsumoto, H, Kurasawa, S, Hamada, M, Okami, Y, Ishizuka, M, Takeuchi, T
• Format: Journal Article
• Language: English
• Published: Japan 1988
• Subjects: Animals; Antibiotics, Antineoplastic - isolation & purification; Antibiotics, Antineoplastic - pharmacology; Azaserine - pharmacology; Fermentation; Humans; Hydroxybutyrates; Macrophages - immunology; Mice; Serine - analogs & derivatives; Serine - isolation & purification; Streptomyces - classification; Streptomyces - metabolism; Tumor Cells, Cultured - drug effects
• ISSN: 0021-8820
• DOI: 10.7164/antibiotics.41.1561

Thrazarine, O-[(3R)-2-diazo-3-hydroxybutyryl)]-L-serine, is a new antitumor antibiotic produced by Streptomyces coerulescens MH802-fF5. Thrazarine was isolated from culture filtrate by Sephadex LH-20 column chromatography and reversed phase HPLC. Thrazarine induced cytolysis of tumor cell lines co-cultured with nonactivated macrophages. This effect was tumor specific because the nontumorigenic cells were not lysed by macrophages in the presence of thrazarine. Thrazarine inhibited DNA synthesis and growth of tumor cells directly. It showed neither antimicrobial activity nor the inhibition of transamidation reactions in contrast to azaserine. Toxicities of thrazarine were much weaker than those of azaserine.