174 



DESCRIPTIONS OF ANTIBIOTICS 



CATEGORY 1 : 



Mixtures of actinomycins for which some com- 

 ponent data have been pul)lished. 



Biosynthetic Acfinoiuycin Mixtures E and F 



Produrecl by: Streptomyces sp. 



Remarks: This organism, whicli normally jjro- 

 duced an actinomycin mixture of the "C type," pro- 

 duced another mixture containing entirely new 

 actinomycins ("E type") when DL-isoleucine was 

 added to the medium. It produced still another 

 mixture ("F type"), along with actinomycins 

 VI(C2) and X'llfCg) when sarcosine was added 

 (58, 59). 



Method of extraction: Actinomycins of the "F 

 mixture" were separated by chromatography on 

 alumina (59). 



Chemical and physical properties: Mixture "E" 

 contains two major component actinomycins, 

 E, and E.>. E, : C = 58.89%; H = 7.21%; N = 12.28%. 

 Specific extinction at 444 nxfx is 18.2 (ethanol). 

 E.2 : C = 52.21%; H = 7.20%; N = 11.9()%. Specific 

 extinction at 444 m/x is 19.0 (ethanol). Infrared 

 spectra of Ei and E2 are given in reference 59. 

 Amino acid content is given in Table 39. The 

 n-methyl isoleucine probably replaces the N- 

 methyl valine of actinomycin VII (Ca). 



"Mixture F" contains six component actino- 

 mycins, Fo to P\>, . All have the same ultraviolet 

 and infrared spectra. Specific extinctions at 444 

 niM (ethanol): Fi = 19.0; F. = 19.4; F:, = 18.5; 

 F4 = 19.0; F., = 17.8 (59). See Table 39 for the amino 

 acid content of the F actinomycins. 



Biological activity: Ei has 90 per cent of the 

 activity of actinomycin VI (C2) against B. siibtilis; 

 E2 , 82 per cent ; Fo , 74 per cent; Fi , 59 per cent; 

 F2 , 71 per cent; F.'j , 47 per cent; F4 , 55 per cent; 

 and F5 , 72 per cent (59). Against Walker carcinoma 

 (rat). El had slight activity; E2, none; Fo was 

 active at 5 X W) jug per kg; Fi , F2 , F3 , and F4 were 

 active at high repeated doses (200 to 1000 /ug per 

 kg); Fo was active at 100 /ig per kg (single dose). 

 Against Jensen sarcoma (rats), Fi (the only one 

 tested) was active. With Yoshida sarcoma (rats) 

 as the test tumor, Fo , Fi , F2 , and F4 were inactive 

 at 6 X 00 Mg per kg (highest level tested). Against 

 Rous sarcoma (chickens), Ei , Ej , Fi , F4 , and F5 

 were active (75). 



Toxicity: Ei , E2, and F, were as toxic as ac- 

 tinomycin IV (D); Fi was 3^ to ^\o as toxic as IV; 

 F2 , H as toxic; F3 and F4 , ^5 as toxic (75). 



Utilization: See reference 75. 



Actinomycin Mixture "A'" 

 Produced by: Streptomyces melanochronKxjcnes 

 (73). 



Method of extraction: Extracted fioni brotli 

 with benzene, and from mycelium with acetone- 

 benzene. Purified by chromatography on alumina 

 (73). 



Chemical and physical properties: Contains three 

 components. Acid hydrolysates of the "mixture" 

 contain threonine, sarcosine, proline, valine, and 

 isoleucine (73). 



Biological activity: Typical of the actinomycins 

 (73). 



Toxicity: No valid data (73). 



Actinomycin Mixture "M" 



Produced by: Streptomyces sp. Has an antimitotic 

 effect (()2a). 



Synonym: "(Jiolitti actinomycin" (63). Prob- 

 ably a mixture of the "B" or "X" type (48, 83). 



Method of extraction: Similar to that of the other 

 actinomycins (63). 



Chemical and physical properties: Has three 

 components with Rf values of 0.2 (trace), 1.0, and 

 1.86, and a fourth variably present (Rf = 2.6) as 

 demonstrated by circular paper chromatography 

 (ethyl acetate-n-butyl ether-2 per cent aqueous 

 naphthalene-2-sulfonic acid, 1:1:2) (63). 



Biological activity: Same as the other actino- 

 mycins (63). For data on the mixtvire see reference 

 74. 



Toxicity: No valid data ((J3). 



Actin4)))iycin P-i 



Synonym: .\ntil)iotic PA I26-P2. 

 Toxicity: Said to be less toxic to animals than 

 actinomycins C and D (107). 



Actinomycin Mixture "Z" 

 Produced by: Streptomyces fradiae (83). 

 Method of extraction: Culture-filtrate extracted 

 with ethyl acetate. Ivxtract concentrated, then 

 evaporated in vacuo to an oily residue. Addition 

 of petroleum ether precipitates Z. Chromato- 

 graphed on aluminum oxide from benzene and 

 developed with l)enzene-absolute CCI4 (65:70), 

 then chloroform-methanol (49:1), followed by the 

 same mixture (19:1). Active fractions concen- 

 trated in vacuo. Residue taken up in acetone. 

 Addition of ether gives "Z mixture." Components 

 separated by chromatography on alumina with 

 benzene as solvent. Developed with chloroform- 

 methanol (99:1) to give Z2, Z3, Z4, and Z.^. Zi fol- 

 lows further elution with same developer, Zn is 

 eluted with CHCU-methanol (97:3). Zo-and Z,- 

 containing fractions are each rechromatographed 

 on alumina. Zi crystallized from acetone-ether. 

 14ie mixure of Z2 , Z3 , and Z4 is never separated. 

 Z5 is also crystallized from acetone-ether (83). 



