Antibiotic and Cytostatic Properties of the Actinomycins

Abstract

Actinomycin was first isolated by Waksman and Woodruff (1940) from a culture of Streptomyces antibioticus. It was found to pose marked antimicrobial properties against gram positive bacteria, and to a lesser extent is active upon gram negative bacteria and fungi. It was later shown to possess selective cytostatic effects upon mammalian tissues (Robinson and Waksman, 1942; Hackmann, 1954). Subsequent studies in various laboratories revealed that actinomycin or actinomycin-like substances are produced by a large number of Streptomyces species. The various forms of actinomycin have been designated as A, B, C, D, I, J, and X (Waksman, 1954). These actinomycins, while readily crystallized, are generally not chromatographically homogeneous substances. In more recent investigations it has been shown that they are mixtures of closely related polypeptides linked to a chromophoric quinonoid moiety (Brockniann, 1954) apparently identical for all the actinomycins (Brockmann and Muxfeldt, 1955). Physical and chemical differences observed among the various actinomycin complexes are considered to be due to variations in the number, arrangement, and kinds of amino acids present in the peptide. For example, actinomycin C can be distinguished from actinomycins A, B, D, I, and X through the presence of D-alloisoleucine in the peptide part of certain of its components. All actinomycin complexes thus far analyzed possess the amino acids sarcosine, D-valine, L-proline, L-threonine, and N-methylvaline. Recently a number of crystalline and chromatographically homogeneous components were separated from the actinomycin complexes, A, B, and D (Roussos and Vining, 1956). Comparison of their chemical and physical properties revealed that these components represented only three distinct entities (

Actinomycin Formation by Streptomyces Cultures1

“…According to the data of Pugh et al (1956), actinomycin A, B, C, and D show comparable activities. Actinomycin X also has activity similar to actinomycin D. Because adequate supplies of actinomycin D were available while only small amounts of the other actinomycins were available, and since their activities against gram positive organisms were all similar, actinomycin D was chosen as the standard.…”

“…In some instances, as with streptomycin (Youmans and Fisher, 1949;Brink and Folkers, 1949) and actidione (Leach et al, 1947;Whiffen, 1948;Leach and Ford, 1948;Kornfeld et al, 1949), these antibiotics are quite dissimilar chemically and biologically; in a number of cases, however, the antibiotics produced by a particular organism are very closely related in chemical structure and biological activity. The penicillins (Clarke et al, 1948;Florey et al, 1949), polymyxins (Long et al, 1949;Craig, 1955), bacitracins (Craig, 1955), and actinomycins (Pugh et al, 1956;Roussos and Vining, 1956) represent examples of families of highly similar substances. In such cases, the difference between related antibiotics may be the presence of a different amino acid or the number of molecules of an amino acid in a peptide chain.…”

Focused Review: Cytotoxic and Antioxidant Potentials of Mangrove-Derived Streptomyces

“…This bacterium produced an active compound with specific bacteriostatic and bactericidal properties which was then designated as actinomycin (Waksman and Woodruff, 1940a , b ). Apart from inhibiting the growth of some pathogenic bacteria and fungi (bacteriostatic), actinomycin or dactinomycin was the first antibiotic shown to possess anticancer activity; the drug was approved by United States Food and Drug Administrative (FDA) in 1964 under the trade name Cosmegen (Waksman and Woodruff, 1940b ; Pugh et al, 1956 ). This valuable drug is currently listed in the 19th WHO Model List of Essential Medicines (April 2015) as a therapeutic agent against gestational trophoblastic neoplasia, rhabdomyosarcoma and also Wilms tumor.…”

Nomenclature of the Actinomycins

“…A study of their biological properties fully confirmed these conclusions. 27 On the basis of these results, Roussos and Vining suggested that the naturally produced actinomycins A, B, X, and D are made up of the same components and that the differences observed may be attributed to the relative amounts cf each produced by the respective Streptomqces species.…”