164 



DESCRIPTIONS OF ANTIBIOTICS 



did not induce any toxic signs when injecletl sul)- 

 cutaneously. 



Reference: 1. Umezawa, H. et al . Japan. J. Med. 

 Sci. tt Biol. 6: 261-268, 1953. 



Actidiiins 



Produced by: Streptomyces sp. 



Method of extraction: Isolated from broth- 

 filtrates and mycelial extracts by acid, or complex 

 precipitation, solvent extraction, or absorption 

 techniques. Purified by solvent precipitation, 

 chromatography, and countercurrent distribution. 



Chemical and physical properties: Complex com- 

 posed of six components, very closely related. 

 Yellow to reddish substances. Darken at 280°C, 

 but do not melt up to 350°C. Insoluble in water and 

 slightly soluble in butanol, ethanol, pyridine, ace- 

 tic acid, cyclohexane, and dimethylformamide. 

 Certain variation exists among the components as 

 to solubility in acetone, methanol, and chloroform. 

 Soluble in strong mineral acids, and are precipi- 

 tated on dilution. Most stable at acid and neutral 

 pH; unstable to alkali. Not readily diffusible. 

 Reineckates: Soluble in acetone. Rf (butanol-ace- 

 tic acid-water, 62:12:26) 0.95 (tail). Infrared data 

 given on components II, III, and VI in reference 1. 

 All give a yellowish fluorescence in organic sol- 

 vents; is less intense in aqueous solvents. Contain 

 C, H, N, and S, and in one case, CI. Acid or alka- 

 line hydrolysates contain a fluorescent acidic 

 product and a ninhydrin-positive material com- 

 posed of a neutral and an acidic fraction. 



Biological activity: Active on gram -positive 

 bacteria. Not active on gram-negative bacteria or 

 mycobacteria. 



Reference: 1. Burton, H. S. Chem. & Ind. 

 442-443, 1955. 



Acliniii 



Produced by: Streptothrix {Streptoutyces) felis. 



Synonym: Mycetin. 



Remarks: Organism isolated from a gramdomat- 

 ous lesion of a cat; pathogenic for various animals. 



Method of extraction: No data. 



Chemical and physical properties: Basic poly- 

 peptide. 



Biological activity: Active (in mice) on Ehrlich 

 adenocarcinoma when administered as the cidture 

 fluid, destroying the tumor completely. DeAngelis 

 (1, 2) claims to have first demonstrated, in 1936, 

 the cancerolytic properties of this culture, and he 

 considers it to be the first antitumor antibiotic. 

 Active on gram-positive and gram-negative 

 bacteria. 



Toxicity: Said to be nontoxic when given in doses 

 which destroy tumors. 



I 'lilization: Is said to have caused complete 

 regression of certain types of cancer in man. 



References: 



1. DeAngelis, (i. Oncologia 2: 43-62, 1949. 



2. DeAngelis, G. Ateneo parmense 28: 248- 



260, 1957. 



Vfliiioholiii 



Produced by: Streptomyces sp. 



Method of extraction: Broth-filtrate adsorbed on 

 Darco G-60 at pH 4.0. Eluted with 30 to 40 per cent 

 aqueous acetone. Eluates adjusted to pH 3.5 and 

 concentrated in vacuo. Chromatographed on 

 Decalso (at pH 6.0) and eluted with 5 per cent 

 aqueous acetic acid containing 10 per cent ethanol. 

 Active fractions adsorbed on a Darco G-60-Celite 

 545 mixture (1:1) and eluted with 20 pei cent 

 aqueous acetone. Active fraction adjusted to pH 

 3.5, concentrated in vacuo, and mixed with 0.02 M 

 cupferron (C6H5N(NO)ONH4) in 50:50 n-butanol- 

 chloroform to remove iron. Aqueous layer washed 

 with chloroform, concentrated in vacuo at pH 3.2, 

 then freeze dried. Purification by salt conversion. 

 Sulfate crystallized from vvater-ethanol (25:45). 

 Occasional difficulties were encountered because 

 of the tendency of actinobolin to form complexes 

 with aluminum (and other Group III elements). 

 Aluminum was removed by oxine precipitation or 

 preferential adsorption on Dowex 50 columns (2). 



Chemical and physical properties: Amphoteric 

 substance. Base is amorphous, white, flufl'y pow- 

 der. Hydrophilic; verj^ soluble in water. Could not 

 be extracted from aqueous solution with any com- 

 mon water-immiscible organic solvent. Basic: 

 1)K;, = 7.5 and a weakly acidic (enolic) pKa = 8.8. 

 Gives a purple color with ninhydrin, red-orange 

 with the Pauly diazo reagent, a red color with 

 FeChi . Positive KMn04 , Fehling, Folin-Cio- 

 calteu, and iodoform tests. Negative Moiisch, 

 I'^hrlich (dimethylaminobenzaldehyde), and Elson- 

 Morgan tests. No reactive carbonyl. Could not be 

 hydrogenated. One N atom per molecule was lib- 

 erated by the Van Slyke procedure; the other N 

 was nonbasic. CnH.o-o.oNaOe-iiHoO: C = 50.31%; 

 H = 6.88%; N = 9.17%. Sulfate: colorless crystals; 

 solul)ilities the same as the base. Ultraviolet ab- 

 sorption spectrum maxima at 263 niyu (a = 26.6) in 

 0.1 N HCl; at 264 m/x (a = 25.3) in 0.1 M phosphate 

 butter at pH 7.0; and at 288 m/x (a = 40.6) in 0.1 N 

 NaOH. Infrared spectrum given in reference 2. 

 Most stable at pH 3.0; unstable at pH 7.0 and 

 above, [a]^ = +54.5° (c = 1 per cent in water). 

 Acetate: white needles, m.p. 263-266° C. Softens 



