Antitumor anthracycline antibiotics, aclacinomycin A and analogues. I. Taxonomy, production, isolation and physicochemical properties.

Abstract

Aclacinomycin A and B, two major components of a new antitumor antibiotic complex, and their 19 analogues were produced by a culture of strain No. MA144-Ml, which was identified as Streptomyces galilaeus. They were isolated by chelation with copper ion and silicic acid chromatography, and characterized by physicochemical methods in the anthracycline group of antibiotics. During the course of screening for new antitumor antibiotics, the cultured broth of an organism MA144-M1, which was isolated from a soil sample collected in Kamiosaki, Shinagawa-ku, Tokyo, Japan, showed marked inhibitory effect on L1210 leukemia in mice. The organism produced a new water-insoluble pigment antibiotic complex named aclacinomycin, which was extracted from the cultured broth and separated into thirteen yellow and seven red-colored components. They belong to the aklavinone and e-pyrromycinone group of anthracyclines, and aclacinomycins A and B1) were produced preferentially. The results of structural studies2~4) indicated that twelve components; Al (aclacinomycin A), BI (aclacinomycin B), Y1 (aclacinomycin Y), Ll (N-monodemethyl aclacinomycin A), G1 (MA144 G1), M1 (MA144 Ml), N1 (MA144 NI), S1 (MA144 S1), TI (1-deoxypyrromycin), El (7,7'-dideoxy-7,7'-biaklavinone), M2 (MA144 M2), and S2 (MA144 S2) were confirmed to be novel compounds. Three yellow components, Cl, D1 and Fl, and five red-colored components, A2, B2, T2, C2 and D2 were identical with 7-deoxyaklavinones), aklavinones"'), bisanhydroakla-vinone7), cinerubin A8), cinerubin B9), pyrromycin10), 7-deoxypyrromycinone (~-pyrromycinone)5), and e-pyrromycinone10), respectively. This paper deals with the taxonomy of the producing organism, the production, isolation and physicochemical properties of aclacinomycin A and its analogues. Taxonomy (1) The Strain MA144-M1 has the following morphological characteristics: Open spirals were observed to develop well from branched substrate mycelia. There were no whorls, and mature spore

Rhodomycin analogues from Streptomyces purpurascens: isolation, characterization and biological activities

“…Aklavinone is the first aglycone during the synthesis of rhodomycin (Connors et al 1990). Aklavinone can be glycosylated by a glycosyl transferase to form Aclacinomycin (Oki et al 1979). Hence the possibility of obtaining aclacinomycins in the fermentation broth of S. purpurascens cannot be denied.…”

Compartmentation of enzymes interconverting aclacinomycins in Streptomyces species AM 33352

“…1987). extracted from the mycelium, and purified to homogeneity by common chemical methods (OKI et al 1975(OKI et al , 1979a(OKI et al , 1979b Strains and conditions of fermentation: Surface cultures of mutants of Strrprornycrs spec. AM 333521s I82 (obtained from the strain collection of the Central Institute of Microbiology and Experimental Therapy, Jena) were used for inoculum preparation employing Soya 2 g medium (g/l; glucose 20, soya meal 20, NaCl 5 , CaCO, 3.…”

Chemical modification of anthracycline antibiotics. I. Demethoxycarbonylation, 10-epimerization and 4-o-methylation of aclacinomycin A.

“…G16 =5'''-epimer of 1) (4) and 7-epi-demethoxycarbonyl MA144 G1 (5). When alkaline treatment of 1 was kept overnight at room temperature, it was converted to demethoxycarbonyl MA 144 S1 (cf.…”