DESCRIPTIONS OF ANTIBIOTICS 



323 



30. Kiiroya, M. J. Antil)iotics (Japan) llA: 



187-192, 1958. 



31. Solotorovsky, M. et al. Antibiotics A 



Chemotherapy 8: 86-92, 1958. 



32. Stammer, C. H. et al. J. Am. Chem. Soc. 



80: 137-140, 1958. 



33. Spencer, C. F. et al. J. Am. Chem. Soc. 



80: 140-143, 1958. 



34. Lawrence, J. C. Brit. J. Pharmacol. 14: 



168-173, 1959. 



35. Celmer, W. D. and Koe, B. K. U. S. Patent 



2,891,051, June 16, 1959. 



Novonij ciii 



Produced bij: Streptomyces roseorhromogenes . 



Method of extraction: Extracted witli the vise of 

 a cation exchange resin. 



Chemical and physical properties: Basic sub- 

 stance. Reineckaie: m.p. 187-188°C. Water-soluble. 

 Positive ninhydrin test. Negative maltol, Molisch, 

 Fehling, FeCls , and biuret tests. Optically inac- 

 tive. Ultraviolet spectrum shows only end-ab- 

 sorption. Differentiated from fradiomycin, nea- 

 mine, and roseomycin by paper chromatography. 



Biological activity: Active on gram-positive and 

 gram-negative bacteria (0.75 to 1.5 ^g per ml) and 

 mycobacteria (1.25 to 2.5 fj,g per ml.). 



Toxicity: LD50 (mice) 667 to 1334 mg p?r kg 

 intravenously. 



Reference: 1. Maeda, K. et al. Japan. J. Bacter- 

 iol. 9:600, 1954. 



Nucleocidiii 



Produced by: Streptomyces calinis (2, 5). 



Method of extraction: Adsorbed from broth on a 

 Darco G-60-Celite 545 mixture at pH 7.0. Ehited 

 with 95 per cent aciueous acetone, acidic or basic 

 alcohols, aqueous acidic alcohols, "Cellosolves." 

 or dilute acids. Eluate concentrated in vacuo to a 

 small volume, then (a) lyophilized; or (b) tak'ui up 

 in 50 per cent aqueous acetone and chronuito- 

 graphed on activated charcoal or charcoal-Celite; 

 or (c) washed with butanol at pH 2.0, adjusted to 

 1)H 7.0, saturated with ammonium sulfate, and 

 extracted with butanol. Butanol concentrated to 

 remove the solvent, and residue lyophilized. 

 Chromatograi)hed from butanol -saturated water 

 mi.xed with diatomaceous earth at pH 2.0 on Celite 

 and developed with almost water-saturated bu- 

 tanol. Crystallized from dilute aqueous solution at 

 pH 4.0 by cooling to 4-5°C and seeding. Can also 

 be extracted from an ammonium sulfate-saturated 

 broth with n-butanol or acetone (1, 5). 



Chemical and physical properties: Amphoteric 

 (1) or weakly basic (4) substance. White, thread- 



0.1 N NacH 259 m^ ^E\l,, 406); X?,;L^ "'"' 255 to 257 

 392); xrax"'""'* 256 m^ (« = 15,500). 



like crystals. Soluble in methanol, acetone, and 

 water at pH 9.2 and 3.2. Less soluble in water at 

 pH6.5. Slightly soluble in n-butanol, ethyl acetate 

 and benzene; practically insoluble in ether 

 X 



m/i (E 



Infrared spectrum given in references 1 and 5. 

 [a]'D ' = —33.3° (c = 1 .05 per cent in a 1 : 1 ethanol- 

 0.1 X HCl mixture). Stable at pH 3, 7, and 9 at 

 room temperature for 24 hours. Destroyed by 

 boiling. CuHis-ieNeOsS: C = 34.03%; H = 4.05%; 

 N = 21.60%; S = 8.30%; OCH., = 0%; N— CH., 

 = 0%; (1, 5). Hydrolysis with ethanolic HCl 

 yields adenine. Nucleocidin may be the 

 glj'coside of adenine in which sulfamic acid is 

 bound to the carbohydrate moiety as an ester. 

 Partial structure (4) : 



NH,, 



^N' 



N, 



■^N' 



)CH 



-C«H,„0. 



-0— S— NH, 



Picrate: Bright yellow crystals; m.p. 143-144°C 

 (uncorrected, slight decomposition). Xmix^ 253 and 

 356 m^. Forms a white hydrochloride, an amor- 

 phous sulfate, and a colored crystalline heli- 

 anthate (5). 



Biological activity: Active in vitm on gram- 

 positive anil gram-negative bacteria, inchuling 

 mycobacteria, Pseudomonas, and Erwiniu. Active 

 on Endamoeba histolytica. Active in vivo on 

 Trypanosoma equiperdiim infections in mice and 

 rats, but not on Streptococcus pyogenes infections 

 (1,3,5). 



Toxicity: Very toxic. LD^j (mice) 0.2 mg per kg 

 intraperitoneally (1). 



References: 



1. Thomas, S. O. et al. .\ntibiotics Ann. 716- 



729, 1956-1957. 



2. Backus, E. J. et al. Antibiotics & Chemo- 



therapy 7:532-541, 1957. 



3. Tobie, E. J. J. Parasitol. U: 291-293, 1957. 



4. Waller, C. W. et al. J. Am. Chem. Soc. 79: 



1011-1012, 1957. 



5. British Patent 815,381, June, 24, 1959. 



Nyboniycin 



Produced by: Streptomyces sp. (1, 2). 



Method of extraction: I. Washed mycelium 

 extracted with boiling 95 per cent ethanol; the 

 extracts dried in vacuo. Impurities removed with 



