DESCRIPTIONS OF ANTIBIOTICS 



233 



Biological activity: Active against mycobacteria, 

 7v. pneuDioniae, and B. subtilis. Cross-resistance 

 with neomycin and viomycin, but ciuantitatively 

 different from neomycin (3). 



Toxicity: LD50 (mice) 125 mg per kg intraven- 

 ously. Causes neurotoxicity in cats. Toxic to duck- 

 weed (Lemna minor) at 1 ppm (2). Causes wheat 

 root tip ehmgation in taj) water sohition at 0.1 

 ppm (4). 



References: 



1. Davisson, J. W. Antibiotics & Chemotlier- 



apy 2: 460-462, 1952. 



2. Nickell, L. G. and Finhiy, A. C. J. Agr. 



FoodChem. 2:178-182,1954. 



3. Szybalski, W. and Bryson, V. Am. Rev. 



Tuberc. 69: 267-269, 1954. 



4. Barton, L. X. and MacNab, J. Contrib. 



Boyce Thompson Inst. 17: 419, 1954. 



Celesticelin 



Produced by: Strepto)iiyces caelesfis (3). 



Synonym: Antibiotic D 52 (3). 



Method of extraction: Extraction of the filtered 

 broth with methylene chloride at pH 7.8. Concen- 

 tration of the extract. Addition of petroleum ether 

 to the concentrate precipitates crude celesticelin 

 as a tan solid. Oxalic acid or salicylic acid added 

 to the methanolic solutions of celesticelin. The 

 oxalate or salicylate formed is purified l)y re- 

 crystallization. Reconversion of the salts to the 

 amorphous free base accomplished by extracting 

 their aqueous solutions at pH 7.5 with methylene 

 chloride. Also can be extracted from broth with 

 ethyl or amyl acetate, or butanol. Extract concen- 

 trated. Concentrate added to hexane to give 

 amorphous celesticelin. Can also be precipitated 

 or isolated from the organic extract of l)roth as 

 the salt of an acid. Purification or initial extrac- 

 tion can also be accomplished by adsorption on 

 alumina, silica gel, activated clays, or acetic acid- 

 treated charcoal. Elution with a polar organic 

 solvent in which celesticelin is soluble (3). 



Chemical and physical properties: Amphoteric, 

 colorless, amorphous substance. pKa of basic 

 group, 7.7; pKa of acidic group, 9.8. Soluble in 

 acidic and strongly basic aqueous solutions. In 

 soluble in water between pH 7 and 10. Soluble in 

 polar solvents, l)ut insoluble in ether or light hy- 

 drocarbons. Stable between pH 5 and 7 for 60 

 days or longer at 24°C. [afo for the free base = 

 4-126.6° (c = 0.5 per cent in chloroform). Maximal 

 vdtraviolet light absorption in 0.01 A^ alcoholic 

 potassium hydroxide at 248 and 341 m/x; in 0.01 N 

 alcoholic sulfuric acid at 240 and 310 m/x. Positive 

 FeCl-i , Molisch, and Ekkert tests. Formation of 



white precipitates with bromine water, Millon's 

 reagent, and mercuric chloride. No precipitation 

 with silver nitrate or lead acetate. Negative Bene- 

 dict, ninhydrin, and iodoform tests. C = 54.87%; 

 H = 6.75%; N = 5.30%; S = 6.02%. Empirical 

 formula: C-24H:i6N209S. Hydrochloride: White semi- 

 crystalline powder. [a]o = -|-96.7° (c = 0.5 per 

 cent in water). Oxalate: White needles; m.p. 149- 

 154°C. [af^ = -1-106.4° (c = 0.5 per cent in water). 

 Indefinite benzenesulfonyl chloride test. Negative 

 nitroprusside, FeClg (brown), and l)romine in 

 CCI4 tests. Positive NaN.3-l2 test (for C— CH or 

 C^S). Salicylate: Crystals; m.p. 136-138°C. 

 [a]l^ = +90.2° (c = 0.5 per cent in water). All 

 salts have essentially the same ultraviolet spec- 

 trum as the base (3). Mild alkaline hydrolysis 

 yields salicylic acid and a basic product, Cn- 

 II32N2O7S, called desalicetin. Acid hydrolysis 

 yields, among other products, L-hygric acid and 

 a reducing amino sugar, CgHigHOe , and celestose. 

 Partial struct lu'e of celesticelin (2): 



H S— CH.CH2— O— C- ,, 



\ ^ \ / 



c 



/ \ OH 



HOHC O 



HOHC 



C 



CH- 



CHOH- 



CH, 



CH, NH OCH3 



I 

 C=0 



L 



CH:,-N/ 



Biohnjicul activity: Active in vitro against gram- 

 positive bacteria at the level of 0.19 to 12.5 /xg 

 per ml. Not active against gram-negative bac- 

 teria or fungi. Active in vivo against experimental 

 Streptococcus hemolyticus and Staph, aureus in- 

 fections. Inactive in vivo against M. tuberculosis 

 H37Rv and Newcastle and influenza viruses. Re- 

 ported to enhance the growth of animals and poul- 

 try. Active on plant disea.ses, including fire blight 

 of apple and pear trees, bacterial spot of tomatoes, 

 walnut blight, halo blight of beans, turf diseases, 

 mint rust, and cherry leaf spot. Active in vitro 

 on Xocardia asteroides (3). 



Toxicity: LD50 (mice) 167 mg per kg (free base) ; 

 233 mg per kg (oxalate) intraperitoneally (3). 



References: 



1. DeBoer,C.et al. Antibiotics Ann. 831-841, 

 1954-1955. 



