198 



DESCRIPTIONS OF ANTIBIOTICS 



III l)roniofonn, has little ultraviolet absorption 

 above 270 m^. Infrared data given in reference 2. 

 Positive FeCls (green) reaction. C35H48N4O9 (2). 

 Patent Component B: Solul)le in lower alcohols, 

 ketones, esters, methylene dichloride, acetic acid, 

 tlioxane, and dimethylformamide. Moderately 

 soluble in benzene; slightly soluble in water (2.7 

 mg per ml) and the lower ethers. Insoluble in 

 light petroleum (b.p. 60-80°C) and carbon tetra- 

 chloride. Ultraviolet absorption spectrum maxi- 

 mum at 215 niM (^IL 650) (ethanol). Infrared 

 spectrum given in reference 5. [a]; = —17.4° 

 (c = 0.4 per cent in methanol). C = 63.25%; H = 

 7.10%; N = 8.05%; O = 21.60%. Molecular weight, 

 650. From these figures the formula C34H46O9N4 

 may be calculated (5). All -patent components: 

 Data on Rf values on paper chromatography given 

 in reference 5. 



Biological activity: Complex: Active in vitro on 

 gram-positive bacteria, including Staph, aureus, 

 Sarcina lutea, and B. subtilis (3). Most active at 

 pH 5.5 to 7.5; less active at pH 8.5. Resistance to 

 E 129 develops more slowly than to erythromycin, 

 spiramycin, novobiocin, or vancomycin. Partial 

 cross-re.sistance with erythromycin and spiramy- 

 cin (1). Patent Component B: Active on the same 

 organisms as the complex at 0.32 to 20 /xg per ml 

 (5). Complex: Active in mice on Streptococcus hemo- 

 lijticus /3 infections (3). Relationship of the compo- 

 nents: G mixed with eciual quantities of "Other 

 Component B" is six times as potent as A. Alone, 

 all three are relatively inactive. Mixtures of A 

 and ''Other Component 5".- B potentiates an equal 

 weight of A; any excess of A over B acts as an inert 

 diluent. Mixtures of "Other Component 7?" and G: 

 B potentiates an equal weight of G; any excess of 

 one factor over the other acts as an inert diluent. 

 Mixtures of A, "Other Component B," and G (not 

 containing a large excess of B over G) : Any B pres- 

 ent preferentially potentiates an equal weight of 

 G. Only when there is more B than G is any B 

 available to potentiate A (3). 



Toxicity: Complex: Nontoxic to mice at thera- 

 peutic levels (2). 



Utilization: As effective as erythromycin on 

 furunculosis (4). 



References: 



1. Garrod, L. P. and Waterworth, P. M. Brit. 



Med. J. 2: 61-65, 1956. 



2. Ball, S. et al. Biochem. J. 68: 24P, 1958. 



3. Bes.sell, C. J. et al. Biochem. J. 6«: 24P- 



25P, 1958. 



4. Scott, A. and Waterworth, P. M. Brit . Med. 



J. 2: 83-84, 1958. 



5. Ball, S. and Hughes, I. W. British Patent 



799,053, Julv 30, 1958. 



Aiilihiolic K MM 



Produced by: Streptomyces sp. 



Method of extraction: Adsorption of active sub- 

 stance from broth-filtrate on lonex-C (H+) resin 

 at pH 7.2. Elution with 80 per cent aqueous ace- 

 tone. Eluate evaporated in vacuo. Aqueous residue 

 extracted with ethyl acetate at pH 7.2. Extract 

 evaporated to dryness in vacuo. Syrup dissolved 

 in ethanol and precipitated with cold water at 

 pH 2.0. Chromatographed on alimiimi from an 

 ether solution and eluted with ether. 



Chemical and physical properties: Brownish 

 powder. Soluble in methanol, ethanol, butanol, 

 amyl alcohol, acetone, ethyl acetate, chloroform, 

 dichloroethylene, and ether. Insoluble in petro- 

 leum ether, benzene, and distilled water. Stable 

 to boiling for 20 minutes at pH 2.0 to 9.0. Ultra- 

 violet absorption maximum at 230 to 235 m/x (c = 

 0.1 per cent in aqueous methanol). 



Biological activity: Not active on bacteria, fungi, 

 or yeasts except B. anlhracis (weak activity). Ac- 

 tive in tissue culture on influenza PR 8 virus, pos- 

 sibly inhibiting intracellular growth (1, 2); also 

 active on PR 8 in ovo but not in mice (3). 



Toxicity: LD;,o (mice) 100 mg per kg iiitraperi- 

 toneally. 



References: 



1. Higo, N. et al. JaiKin. J. Microbiol. 1: 91- 



97, 1957. 



2. Miyakawa, J. et ul. Japan. J. Microbiol. 



2: 53-62, 1958. 



3. Hinuma, Y. et al. Japan. J. Microbiol. 2: 



63-68, 1958. 



Antibiotic EI5 



Produced t)y: Streptomyces sp. having gray spores 

 and differing from S. griseus, S. lavendulae, and 

 the actinorul)in -producer. 



Synonym: Possibly related to actinoruliin 

 (streptothricin-type substance) . 



Method of extraction: Adsorbed from broth-ttl- 

 trate on carbon. p]hited with acid-methanol and 

 precipitated on addition of acetone. Purified l)y 

 chromatography on Decalso or on IRC-50. Elu- 

 ates concentrated in vacuo and precipitated with 

 acetone. 



Chemical and physical properties: Acid salt: 

 White substance. Soluble in water and acid- 

 methanol. Insoluble in ether and acetone. Thermo- 

 stable (resists boiling). 



Biological activity: Similar to actinorubin. 

 Strains of bacteria made resistant to EIr, were also 

 resistant to stre))tothricin, but the reverse was 

 not uniformly true. 



