DESCRIPTIONS OF ANTIBIOTICS 



173 



trace components including Co, Cna, Cia, Csa, 

 Csa , and C4 (36, 37, 87). These components have 

 the following Rcj values (Rf value relative to 

 actinomycin VI(Co)) (87):Cu = 0.2; VICC.) = 1.0; 

 C3a = 1.56; IV (CO = 0.69; C-a = 1.15; C4 = 1.7 ; 

 Cia = 0.8; VII (Ca) = 1.39. System: n-Dibutyl 

 ether, n-butanol, and 5 per cent aqueous /3-naph- 

 thalene sulfonic acid. Other components have 

 been reported formed when a "C mixture"-pro- 

 ducing streptomycete was grown in the presence 

 of various amino acids (64) (see actinomycin 

 mixtures E and F). The infrared spectrum of 

 actinomycin IV (Ci) is given in reference 36 and 

 that of actinomycin VII (C3) in reference 37. The 

 other physical and chemical properties of actino- 

 mycins IV (Ci), VKC.), and VII(C3) are given in 

 Table 40. Their amino acid content is given in 

 Table 39 (24, 77). On mild acid hydrolysis, actino- 

 mycin VII (Cs) splits off one molecule of ammonia 

 andformsa "desamino actinomycin" (C64H89O17N11 ; 

 brick-red rhomboid crystals; m.p. 239°C). The 

 chromophore of this degradation product (3 hy- 

 droxy! , 8 dimethylphenoxazone- (2) -dicarboxylic 

 acid- (4, 5) (40) is shown below: 



COOH 

 OH 



"AA-AC mixture", contains two actinomycins 

 in major amounts, IV (AA) and VII(AC), and a 

 minor component with an amino acid content 

 like that of VII, but not as yet completely char- 

 acterized (30, 33, 83). References giving data 

 concerning the "mixtures" include 16, 29, 36, 37, 

 40 ("C mixture"); and 14, 30, and 33 ("AA-AC 

 mixture") . 



Biological activity: The minimal inhibitory con- 

 centrations of some of the component actinomycins 

 of the "C mixture" against/^, suhtilisare as follows 

 (in ;ug per ml): actinomycin IV (Ci), 0.2; VI (C.), 

 0.14; VII (C3), 0.2; C«, 19; Cja, 50; and C<>3, 28. 

 The activity against mammary carcinoma TM 

 8013 and lymphosarcoma T 24 179 of the "C mix- 

 ture" is accounted for by actinomycins IV (Ci), 

 VI(C2), and VII(C3); VII (C3) being the least 

 active (67). "Desaminoactinomycin" has less than 

 Koo the activity of the parent compound on 

 Staph, aureus (40). References giving data on the 

 biological activity of the "C mixture" include 11, 

 27, 34, 89, and 91; for the "AA-AC mixture," ref- 

 erence 5. 



Toxicity: lA)^ (mice, no route given, mg per 



kg): IV (Ci), 1.8; VI (C), 0.9; VII (C3), 1.6; C„ , 

 8; Coa, 24; and Co(3, 41 (67). References giving data 

 on the toxicity of the "mixtures" include 5 and 27. 

 Utilization: Same as previous "mixtures." See 

 references 41-43 and 49. Some anti-allergy activ- 

 ity has been rei)orted (,42). 



Actinoinyciti H or ./■> 



A preparation designated as actinomycin J2 

 is a mixture of actinomycin Ji and duodecyl ester 

 of 5-ketostearic acid. The last compound has no 

 antibiotic activity. Actinomycin J 2 is very prob- 

 ably the equivalent of Waksman and Woodruff's 

 actinomycin B. Later Waksman, CJeiger, and 

 Reynolds proposed dropping the term actinomycin 

 B to designate this fraction, since obviously it is 

 nothing else than a mixture of actinomycin A 

 with inert material. They proposed calling ac- 

 tinomycin A, actinomycin (1, 105, 106). 



Acli noiiiyriti Mixture "7" 



Produced by: Strcptonryccs parvullus (71, 72), 

 S. antibioticus (99), and Streptomyces sp. (38). 



Synonym: This mixture may contain the same 

 actinomycins as the "C mixture," but in different 

 proportions (77). 



Method of extraction: Xo data. Prol)al)ly the 

 same as for the other "mixtures" described. 



Chemical and physical properties: Contains one 

 major com])onent, actinomycin IV (Ii), and four 

 le.ss well described comj^onents, lo , loa , I2 , and I3 

 (37, 77). Chemical and physical data on actino- 

 mycin IV(Ii) are given in Table 40. The amino 

 acid content of IV (Ii) and lo is given in Table 39. 

 In : Hexagonal bipyramids of needles; m.p. 242 to 

 243°C. Specific extinction at 446 m/x = 20.5 (cyclo- 

 hexane) (37). 



The actinomycins described below have been 

 less well characterized. Whether they contain any 

 of the known actinomycins (I to VII) is a matter 

 for further research. They fall into three cate- 

 gories: Category 1 : Actinomycins which are known 

 to be "mixtures" for which a certain amount of 

 data on the component actinomycins is available. 

 Category 2: "Mixtures" for which no data on the 

 component actinomycins are available. Oidy 

 references to the original papers will be given. 

 Category 3: "Actinomycins" which may be com- 

 posed of one, or more probably, of a mixture of 

 actinomycins. All important data have been in- 

 cluded here, even though subsequent work may 

 show the substance to be a "mixture." In all cases, 

 the original author's terminology has been used. 



