New anthracycline antibiotics.
A number of anthracycline antibiotics have been found in Streptomyces cultures. Among them, adriamycin and daunomycin have been studied most in detail, because these compounds have exhibited a strong antitumor activities 1, 2). However, their clinical usefuleness is limited by side effects, particularly by bone marrow suppression and cumulative dose-dependent cardiac toxicity. 3 approximately 5) By the collaboration with Prof. H. UMEZAWA and Dr. T. TAKEUCHI, Institute of Microbial Chemistry, for the studies to find out new anthracycline antibiotics that may have lower cardiac toxicity and the same degree of the antitumor activity, we found 32 new anthracycline compounds in Streptomyces cultures and aclacinomycin A is under the phase II clinical study. Anthracycline compounds can be classified depending on the structures of their aglycones as shown in Table 1. These compounds have a linear tetracyclic polyhydroxy anthracyclines, and can be grouped into seven groups. Biologically active anthracycline antibiotics have various sugar moieties at C-7 and/or C-10 position of the anthracyclinones. In 1951, H. BROCKMANN6) discovered rhodomycins A and B in the culture of a new species of Streptomyces purpurascens. Since then, he found numerous anthracycline compounds such as rhodomycin-, isorhodomycin- and pyrromycin-types in Streptomyces and elucidated their structures. All of these anthracyclines are red pigments. In 1964 and 1969 new group of orange-red anthracycline antibiotics: daunomycin10) and adriamycin11) was reported by DiMARCO and F. ARCAMONE. Moreover, aklavin12, 13) which has yellow aklavinone as aglycone and citromycinone aglycone14) which is also yellow have been isolated in the Streptomyces cultures. Aclacinomycin A15), which we found in Streptomyces galilaeus MA144-M1, has aklavinone aglycone and is becoming more interesting in its low cardiac toxicity.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000302:isolation & purification / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D006224:Cricetinae; D004285:Dogs; D006027:Glycosides / Q000302:isolation & purification / Q000494:pharmacology; D008297:Male; D051379:Mice; D009279:Naphthacenes / Q000302:isolation & purification / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D006027:Glycosides; D009279:Naphthacenes