268 



DESCRIPTIONS OF ANTIBIOTICS 



11. Magyar, K. ef al. Al)str. C'omimms. Sym- 



posium on Antibiotics, Prague, pp. 26-27, 

 1959. 



12. Kudinova, M. K. Antibiotiki 1(2): 29-33, 



1959. 



13. Brajnikova, M. G. e/ o/. Antibiotiki 4(4): 



29-32, 1959. 



Ett 



usconivcin 



Produced by: Streptomjces lucensis (1, 2). 



Synonym: Antibiotic 1163 F. I. (2). 



Method of extraction: Mycelium and culture- 

 filtrate extracted with n-butanol, methanol, etha- 

 nol, or isopropyl alcohol. Extract concentrated 

 in vacuo to give an active precipitate. Ether added 

 to the mother liquors precipitates a fvuiher active 

 fraction. Purified by washing with acetone, fol- 

 lowed 1)\ liot a<iueous isopropanol ; taking up in 

 anhydrous methanol containing CaClo . Precipi- 

 tated as the base on addition of water. Chroma- 

 tograi)hed on silica gel. Crystallized from water 

 saturated with butanol (1, 3). 



Chemical and physical properties: Amphoteric 

 conjugated tetraene. White crystals. Browns, 

 gradually followed by decomposition at >150°C. 

 Soluble in dimethylformamide, pyridine, glacial 

 acetic acid, and by the formation of salts in acidic 

 or alkaline methanol. Moderately soluble in aque- 

 ous lower alcohols; slightly sokdjle in anhydrous 

 methanol and water; insoluble in acetone, chloro- 

 form, ether, benzene, and other nonpolar solvents. 

 Ultraviolet absorption spectrum maxima at 290, 

 305, and 317 ni/x (E\l'^ about 840, 1385, and 1170). 

 Infrared spectrum given in reference 3. [a\„ = 

 +49.8° (in methanol containing 0.1 A' HCl) ; +296° 

 (pyridine). Gives a red-brown color with sulfuric 

 acid. Positive KMn04 and bromine in carbon 

 tetrachloride tests. Negative FeCl;i and Molisch 

 (weak brown) tests. Stable in the dry state. Lal)ile 

 to heat, light, air, alkali, and acid. Most stal)le in 

 aqueous solution at pH 7.0 (3). Rf values in vari- 

 ous systems of paper chromatography given in 

 reference 3. Broth was reported to contain three 

 components, A, B, and C, all differing in their 

 physicochemical characteristics (2). 



Biological activity: Moderately active on yeasts, 

 fungi, Trichomonas vaginalis, and Endanioeba his- 

 tolytica. Active in vivo (mice) on intestinal Candida 

 infections. Also active (rats) on Endanioeba nniris 

 and intestinal flagellates. Not active on bacteria 



(1). 



Toxicity: LDso (mice) 44.6 mg per kg intraven- 

 ously, 37.1 mg per kg intraperi1on(>ally, and 1263 

 mg per kg orally (1). 



References: 



1. Arcamone, F. et al. Giorn. microbio!. 4: 



119-128, 1957. 



2. DiMarco, A. and Ghione, M. (iiorn. ital. 



chemioterap. 4: 451-461, 1957. 



3. Arcamone, F. and Perego, M. Ann. chim. 



(Rome) 49:345-351,1959. 



Eiiliciii 



Produced by: Streptomyces sp. closely related to 

 S. parvus. This organism also produces an actino- 

 mycin and a basic antibiotic which is active 

 against gram-positive and gram-negative bacteria. 



Method of extraction: I. Adsorption on char- 

 coal, followed by elution with acidic alcohol. II. 

 Adsorption on cation exchange resins and elution 

 with acid. III. Precipitation of antibiotic from 

 culture-filtrate as the insoluble picrate. The crude 

 picrate extracted with methanol; addition of hy- 

 drochloric acid and ether to the methanolic ex- 

 tract precipitates eulicin hydrochloride. The crude 

 hydrochloride is passed through a column of 

 Duolite S-30 resin. Effluent from the column is ti- 

 trated with a solution of methyl orange, resulting 

 in the precipitation of the insoluble helianthate. 

 The helianthate is crystallized and recrystallized 

 from 80 per cent ethanol. Eulicin hydrochloride is 

 obtained by the addition of an excess of hj'dro- 

 chloric acid to methanolic solutions of the helian- 

 thate. The helianthic acid precipitate is removed 

 by filtration, and eidicin hydrochloride is pre- 

 cipitated by adcHtion of ether. 



Chemical and physical properties: Basic sub- 

 stance. HCl salt: White hygroscopic powder. 

 Poorly defined infrared spectrum. Helianthate: 

 Sinters at 142°C; m.p. 154-156°C (decomposition). 

 Free base: Hygroscopic gummy substance decom- 

 posing with release of ammonia within a few hours 

 of preparation. Weakly dextrorotatory. Positive 

 Sakaguchi test. Alkaline hydrolysis products in- 

 clude 9-aminononanoic acid. Acid hydrolysis 

 products include 9-guanidinononanoic acid and 

 "eulicinine," the latter prepared as the helian- 

 thate; m.p. 155-158°C. Structure of (Miiicinine 

 (1,4): 



NH 



H,NCNH(CH2)8CH— CH(CH2)3NH2 



I I 



OH NH. 



The structure of eulicin (C24H62O2N8) is given in 

 Chapter 6. 



Biological activity: Active /// vitro on yeasts and 

 fungi at 0.018 to 5.0 ng, per ml, but only very 

 slightly active (121 ng, \wv ml) on C. albicans. Ac- 

 tive on X. asteroides at 2.3 jug per ml (1, 2). Active 



