312 



i;e8CR1pti()xs of antibiotics 



4. Horowitz, M. I. Thesis, Rutgers University, 



1957. 



5. Tiner, J. I), and Rangaswami, (i. Proc. 



Helminthol. Soc. Wash. I). C. 24: 70-71, 

 1957. 



Mycoliciii 

 Produced by: Streptomyces ruber. 

 Synonym: Similar to fiavofungin. 

 Method of extraction: Yellow pigment extracted 

 from mycelium with warm 95 per cent ethanol. 

 Crystallized by adding water to this solution. 

 Can also be extracted with methanol and crystal- 

 lized from an acetone -water mixture. 



Chemical and physical properties: Yellow cr\\s- 

 tals that fluoresce in ultraviolet light. Inactivated 

 rai)idly by ultraviolet light, losing fluorescence. 

 Storage in dark in vacuo prolongs activity. No N, 



5, or halogens. Negative bromine and potassium 

 permanganate tests; positive test for ketones 

 with dinitrophenylhydrazine sulfate. Reduces 

 ammoniacal silver nitrate and Fehling's solution. 

 Soluble in lower alcohols, propylene and diethyl - 

 ene glycol, sulfuric and phosphoric acids; partly 

 soluble in water, benzene, and acetone; insoluble 

 in ether, petroleum ether, xylene, and chloroform. 

 Dialyzable. Probable formula: C18H30O5 : C = 

 65.90%; H = 9.43%. Ultraviolet absorption max- 

 ima in methanol at 363, 263, and 210 m^. The 363 

 m^ band increases in height with loss of activity, 

 brought about by heating with alcoholic 0.6 A' 

 sulfuric acid, aqueous alcoholic 6 .V hydrochloric 

 acid, and aqueous alcoholic 10 per cent potassium 

 hydroxide on a steam bath for 2 hours; not af- 

 fected by heating with aqueous acetic acid or 

 aqueous alcoholic sodium bicarbonate. Maximal 

 activity at alkaline pH; little or none at pH 2 to 

 5; slight at pH 6 to 7. Antifungal activity unaf- 

 fected by heating at 100°C for 10 minutes at pH 



6. Infrared spectrum in mineral oil gives strong 

 hydroxyl band at 3.1 /jl, medium band at 5.94, 6.2, 

 and 6.34 m- In pyridine, mycoticin gives broad 

 bands at 3.2 to 3.6 and 5.9 to 6.4 yu. A tetraacetyl 

 derivative is formed by adding acetic anhydride 

 and pyridine at room temperature. Melting point 

 of acetate: 140-141°C. C = 63.05 to 63.71%; H = 

 7.62 to 7.93%. Ultraviolet al)sorption maxima 

 for acetate at 361 and 260 m^. Infrared spectrum 

 of acetate in chloroform shows bands at 3.45, 5.75 

 to 5.78, 6.13, 6.3, and 7.95 m/x- Hydrogenation 

 products of antibiotic and acetate are colorless, 

 do not fluoresce, have no ultraviolet maximum 

 and no antifungal activity. 



Biological activity: Active principally on yeasts 

 and some filamentous fungi. Not active on bac- 

 teria or protozoa. 



Toxicity: LDjo (mice) 10 to 20 mg per kg intra- 

 peritoneally. No cutaneous .sensitivity (hiunans) 

 reaction noted in 30 persons tested. 



Reference: 1. Burke, R. C. et al . J. Invest. 

 Dermatol. 23:163-168,1954. 



Myxovironiycin 



Produced by: Streptomyces sp. resembling S. 

 albus (4). 



Remarks: This culture produces seven antibi- 

 otics, inclucUng toyocamycin and actinoflocin (2). 



Method of extraction: Broth adjusted to pH 4.0 

 and filtered. Filtrate adjusted to pH 7.6 and active 

 fraction adsorbed on IRC-50 (H+ form). Eluted 

 with 0.2 A' HCl. Active fractions collected and 

 concentrated in vacuo at pH 4.0. Treated with 

 butanol at pH 8.0 to remove other antibiotics. 

 Aqueous layer concentrated to dryness at pH 4.0. 

 Extracted with acidic methanol and precipitated 

 with acetone. Purification by chromatography on 

 a carbon-diatomaceous earth mixture (6:4) at 

 pH 7.0 from water. Developed with 2 per cent 

 aqueous acetone (1). 



Chemical and physical properties: Basic sub- 

 stance. Reineckate: Crystalline platelets; m.p. 

 184-189°C (1) or 206-209°C (3). Soluble in water 

 and methanol. Insoluble in most other organic 

 solvents. Infrared spectrum given in reference 1. 

 C = 24.53%; H = 4.22%; N = 24.55%; S = 29.1%; 

 Cr = 13.02%. Hydrochloride: m.p. 183-185°C (4). 

 Conflicting reports on ninhydrin and biuret tests 

 (1,3). Yellow color with Pauly test (3). Negative 

 Sakaguchi, Fehling, Molisch, Millon, FeCls , 

 maltol, and Elson-Morgan tests. Only end-ab- 

 sorption of ultraviolet light. [«]„ = +2.8° (c = 

 1.06 per cent in water). Stable at pH 2.0 to 5.0, 

 l)ut not at alkaline pH. Hydrolysis products in- 

 clude /3-alanine and methionine or valine (1, 3). 



Biological activity: Active on influenza A virus 

 in tissue culture, mice, and eggs. Possibly inhibits 

 intracellular growth of the virus. Active in con- 

 tact tests against influenza A (FAI-1), influenza B 

 (Lee), Newcastle disease virus, and the HVJ 

 (hemagglutinating virus of Japan or Sendai virus). 

 No activity on bacteria, fungi, or yeasts, except 

 some mild activity on Sarcina lutea and B. subtilis 

 (1,2,5,6-8). 



Toxicity: LDso (mice) >200 mg per kg (1) or 

 37.5 to 50 mg per kg (3) intraperitoneally. 



References: 



1. Kuroya, M. et al. Japan. J. Microbiol. 1: 



85-90, 1957. 



2. Katagiri, K. et al. Shionogi Kenkyusho 



Nempo 7: 715-723, 1957. 



3. Kobayashi, N. Chemotherapy 5: 149-150, 



1957. 



