214 



DESCRITTIOXS OF AXTIBIOTICS 



the mycelial phase (5). Active //( vivo (mice) on 

 experimental histoplasmosis l)ut not torulosis 

 (Cryptococcus neoformans) (1, 3). Antifungal ac- 

 tivity in vitro suppressed by unsaturated, l)ut not 

 saturated, fatty acids, and Tween 80 (2). 



Toxicity: LDio (mice) 8.6 mg per kg (crude sub- 

 stance) (1), or 18 to 22 mg per kg intraperitone- 

 ally (5), 12.5 mg per kg intravenously. Intra- 

 venous administration accompanied by vestil)ular 

 disturbances and nerve cell degeneration in brain 

 nuclei (1). 



Utilization: Active on tinea capitis in chiltlren 



((i). 

 References: 



1. Hickey, R. J. et al. Antibiotics A: Chemo- 



therapy 2: 472-483, 1952. 



2. Hickey, R. J. Arch. Biochem. Biophys. 



46: 331-33(), 1953. 



3. Emmons, C. W. and Haberman, R. T. Anti- 



biotics ct Chemotherapy 3: 1204-1210, 

 1953. 



4. Vining, L. C. e< a/. 8th Congr. intern, botan., 



Paris Vol. prelim. Sect. 24, 106-110, 1954. 



5. Cohen, I. R. U. S. Patent 2,723,216, Novem- 



ber 8, 1955. 



6. Lubowe, I. I. et al. Antibiotics Ann. 135- 



139, 1956-1957. 



A spar loci II 



Produced by: Streptoniyces griseus var. spiralis, 

 S. violaceus. 



Synonym: Similar to amphomycin. 



Method of extraction: To the culture are added 

 1 gm of calcium chloride per liter and some Hyflo 

 Super-Cel. pH adjusted to 5.0 to 5.5 with hydro- 

 chloric acid; the mixture then stirred and filtered. 

 Cake is washed with water and suspended in 

 water, the pH of which is adjusted to 9.7 to 10. 

 Insoluble materials discarded. Alkaline extract 

 adjusted to pH 1.0 to 2.0 and extracted with 

 n-butanol. Neutralized butanol is concentrated, 

 and calcium chloride added. pH adjusted to 5.0 

 to 5.5, and the white microcrj-stalline calcium 

 salt of aspartocin removed by centrifugation, 

 w-ashed with wet butanol, then washed with ace- 

 tone, and air dried (1). 



Chemical and physical properties: Acidic pol}'- 

 peptide with a fatty acid moiety. C = 53.36%; 

 H = 7.51%; N = 13.36%; S = 0.42%,; CI = 0.07%; 

 ash = 0.62%:; NH. (Van Slyke) = 4.27%,. No 

 characteristic light-absorption spectra. [a]l = 

 +26.4° (c = 2.1 per cent in methanol). More than 

 50 mg per ml of aspartocin will go into solution 

 in methanol, ethanol, or glacial acetic acid. Dis- 

 solves slowly in water or n-butanol. Relatively 

 insoluble in acetone or ethyl acetate. More readily 



.soluble in water at pH <3.0 or >3.6. At pH 3.3, 

 calcium chloride helps to dissolve the antibiotic, 

 and sodium chloride precipitates it. At pH 3, 6 

 per cent of the activity is left after 30 minutes at 

 1()()°C; at pH 5.0, 72 per cent of the activity re- 

 mains. Other pH values are intermediate. As- 

 l)artocin can be separated from amphomycin by 

 chromatography and electrophoresis. Positive 

 biuret test. Rapid uptake of bromine and de- 

 colorization of potassium permanganate. Negative 

 ^Nlillon, xanthoproteic, Sakaguchi, tryptophan 

 (Tillman-Alt), sodium nitroprusside, Molisch, and 

 anthrone tests. Acid hydrolysates ninhydrin-posi- 

 tive and contain an oil which has the properties 

 of an unsaturated fatty acid. Paper chroma- 

 tography revealed seven ninhydrin-positive com- 

 ponents in the acid hydrolysate. Four were identi- 

 fied by bioassays and paper chromatography a.s^ 

 aspartic acid (35 per cent), glycine (10 per cent), 

 L-proline (8 per cent), and L-valine (8 per cent). 

 Also characterized by the hydrolysates were: 

 D-a-pipecolic acid, a(L)iS-methyl aspartic acid, 

 and a-)3-diaminobutyric acid (4). 



Biological activity: Active against gram-positive 

 l)ut not against gram-negative liacteria. Four to 

 eight times more active than amphomycin against 

 B. subtilis and Corynehacterium xerosis. Activity 

 reduced in vitro by inorganic phosphates, and in- 

 creased by calcium ions. Development of re- 

 sistance slow. Cross-resistance with amphomycin 

 (2). Effective in mice infected with Staph, aureus ^ 

 Streptococcus pyogenes, and D. pneumoniae when 

 administered intraperitoneally, subcutaneously, 

 or intravenously; not effective orally (3). 



Toxicity: LDso (mice) 110 mg per kg intraperi- 

 toneally, 200 mg per kg subcutaneously, 120 mg 

 per kg intravenously (3). 



References: 



1. Shay, A. J. et al . Antibiotics Ann. 194- 



198, 1959-1960. 



2. Kirsch, E. J. et al. Antibiotics Ann. 205- 



212, 1959-1960. 



3. Redin, G. S. and McCoy, M. E. Antibiotics 



Ann. 213-219, 1959-1<)60. 



4. Martin, J. H. et al. J. Am. Chem. Soc. 82: 



2079, 1960. 



Aiireofaciii 



Produced by: Streptoniyces aureofaciens. This 

 culture also produces chlortetracycline. 



Synonyms: Prol)ably the same as antibiotic 

 AYF and ayfactin. 



Method of extraction: Mycelium extracted with 

 methanol. Extracts combined and concentrated 

 in vacuo to precipitate aureofacin. 



Chemical and physical properties: Heptaene. 



