260 



Di<:sc'uirTi()xy of antibiotics 



BioUxjicdl (irtivitij: Active against gram-positive, 

 gram negative, and acid-fast bacteria, protozoa, 

 and viruses. Some caiicerolytic activity. Active 

 in vivo against Trypanosoma cfjuipcrdion and T. 

 brucci infections in mice (CJ)on about 0.30 mg per 

 kg subcutaneously). Local antit richomonal ac- 

 tivity (1). 



Toxicity: Toxic to young chicks a1 0.01 per cent 

 in diet (4). LD50 (mice) 3.8 mg per kg subcutane- 

 ously, 0.75 mg per kg intra-abdominally, >2500 

 mg per kg orally (Ij, 0.4 mg i)er kg intraperitone- 

 ally (2). 



References: 



1. Schnitzer, R. J. Ann. N. Y. Acad. Sci. 00: 



1090-1092, 1952. 



2. Corbaz, R. et al. Helv. Chim. Acta 40: 



199-204, 1957. 



3. Keller-Schierlein, W. and Prelog, V. Helv. 



Chim. Acta 40: 205-210, 1957. 



4. Berger, J. et al. Experientia 1."}: 434-436, 



1957. 



5. Ishihara, S. et al. J. Antiljiotics (Japan) 



UA: 160-161, 1958. 



6. Keller-Schierlein, W. et al. Helv. Chim. 



Acta 42: 305-322, 1959. 



Echinomycin-like Antibiotic 



Produced by: Streptoniyces sp. (1) differing from 

 echinomycin-i)rodvicer. 



Synonym: Antibiotic X 1008 (1). 



Method of extraction: Whole broth extracted with 

 butanol. Extract concentrated in vacuo. Anti- 

 biotic precipitated with petroleum ether. Suc- 

 cessively extracted into methylene chloride and 

 methanol, then crystallized from an ethanol-aceto- 

 nitrile mixture (1). 



Chemical and physical properties: Cube-like 

 crystals; m.p. 209-216°C (decomposition), [aj^ = 

 — 282° (c = 1 per cent in chloroform), (lives a 

 melting point depression when mixed with echino- 

 mycin. Same ultraviolet spectrum as echinomycin. 

 Infrared spectrum differs in certain details from 

 that of echinomycin. C29H38O7N6S: C = 56.40%; 

 H = 6.52%; N = 13.69%; S = 5.08%. The side 

 chain attached to the quinoxaline residue probably 

 differs from echinomycin (1). 



Biological activity: Same in vitro antibacterial 

 activity as echinomycin. No trypanocidal activity 

 in mice. Only jiartial cross-resistance with echino- 

 mycin. 



Toxicity: Highly toxic (1). 



Reference: 1. Berger, J. cl al. I'^xpericMitia I.'): 

 434-436, 1957. 



Elirlicliin 



Produced by: Streptomyces lavendulae. 



Method of extraction: Culture-filtrate adjusted 

 to pH 2.0 with concentrated HCl. A dark brown 

 precipitate collected by centrifugation. 



Chemical and physical properties: Stable at neu- 

 trality and alkaline pH. Nondialyzable. Inac- 

 tivated in vitro \>y horse serum. Unaffected \^y 

 tryptic digestion. 



Biological activity: Inhibitory to influenza A 

 and influenza B /// vitro. Active in vivo against 

 influenza B. Inactive against bacteria, fungi, 

 Chlamydozoaceae, pox viruses, and bacterial 

 viruses. 



Toxicity: LDn (mice) 100 mg per kg intra])eri- 

 toneally, 300 mg per kg subcutaneously. 



Reference: 1. Groupe, V. et al. J. Immunol. 

 67: 471-482, 1951. 



Elaioniycin 



Produced by: Streptomyces gelaticiis (4) initially 

 identified as S. hepaticus (1, 3); Streptomyces sp. 

 (5). 



Synomjm: Identical to or closely related to 

 hygroscopin A. 



Method of extraction: I. Broth-filtrate extracted 

 with ethyl acetate at pH 7.0. Extract concentrated 

 in vacuo. Residue successively extracted with 

 water. Extract filtered, and extracted with petro- 

 leum ether at pH 7.0. Solvent removed in vacuo 

 and residual oil extracted with ether. Ether dis- 

 tilled off and oily residue subjected to molecular 

 distillation at pressures of <1 m at 60-61 °C. Puri- 

 fied by countercurrent distribution (n-heptane- 

 methanol-water containing 0.125 per cent (by 

 weight) Na2S04 ; 1.25:1.25:1). Active fractions 

 concentrated in vacuo at 37°C. Residue saturated 

 with NaCl and extracted with n-heptane. Extract 

 concentrated in vacuo and residue sulijected to 

 molecular distillation to give elaioniycin. II. 

 Residue from ethyl acetate-extract of Ijroth (see I) 

 extracted with n-heptane. Upper phase solvent 

 removed by evaporation in vacuo. Residue purified 

 by chromatography on HCl-washed alumina ad- 

 justed to pH 4.5, using multiple absorption col- 

 mnns in series, and n-heptane as solvent and 

 developer. Eluted with ether or methanol. Oily 

 residue after removal of solvent from active frac- 

 tions is subjected to molecidar distillation (1, 3). 



Chemical and physical properties: Slightly yellow 

 oil. Soluble in all common organic solvents but 

 sparingly soluble in water. Ultraviolet absorption 

 spectrum maximum (methanol) 237.5 m/u (e = 

 11,000), remaining unchanged in polar and non- 



