248 



DESCRIPTIONS OF ANTIBIOTICS 



methanol. Extract concentrated in mciin to pre- 

 cipitation. Precipitate dried, washed with aljso- 

 lute ethanol, and taken up in 90 per cent acetone. 

 Solution concentrated, filtered if necessary, and 

 reconcentrated to precipitate the antibiotic. 



Chemical and physical properties: Hexaene. 

 Crystalline; m.p. 100-1 15°C (with foaming). Very 

 soluble in 0.01 iV NaOH and 80 per cent acetone; 

 soluble in methanol; scarcely soluble in water, 

 ethanol, and acetone. Ultraviolet absorption spec- 

 trum shows major maxima at 341 (E'lcin 380), 358 

 (£'lcm 585), and 380 m^ (£'icm 605), and minor peaks 

 at 290, 305, and 320 m//. Negative biuret, Saka- 

 guchi, Molisch, Fehling, ninhydrin, and FeCls 

 tests. Dark blue in H2SO4 . Yellow in acidic solu- 

 tion, slowly becoming brown at alkaline pH. Loses 

 40 per cent of activity in 0.01 .V NaOH at 100°C 

 for 5 minutes. Stable at the same pH for 5 hours 

 at 5°C. Paper chromatographic behavior given in 

 reference 1. 



Biological activity: Active on Staph, aureus at 

 0.8 Mg per ml, B. subtilis at 12.5 ng per ml, Candida 

 iitilis at 1.2 /.tg per ml, and P. chrysogenuni at 6.0 

 fj.g per ml. 



Toxicity: LD50 (mice) 135 mg per kg orally, >10 

 mg per kg intravenously. 



Reference: 1. Sakamoto, J. M. J. J. Antibiotics 

 (Japan) 12A: 21-23, 1959. 



Crystalloniyciii 



Produced by: Streptomyces violaceoniger var. 

 cristallomicini (1). 



Synonym: Similar to amphomycin. Crystallo- 

 mycin differs from amphomycin in that (a) it is 

 more active against experimental pneumococcal 

 infections, and (b) it has more antibacterial activ- 

 ity in liciuid media. Complete cross-resistance was 

 not observed between these two substances (1). 



Toxicity: LD50 (mice) 124 mg per kg intrave- 

 nously, 109 mg per kg intraperitoneally, 220 mg 

 per kg subcutaneously, and over 1500 mg per kg 

 orally (2). Pharmacological data given in reference 

 2. 



References: 



1. Shorin, V. A. and Shapovalova, S. P. Anti- 



biotiki 4(1): 77-81, 1959. 



2. (ioldberg, L. E. Antilnoliki 1(1): 03-66, 



1959. 



Cyanonij ciii 



Produced by: Streptomyces cyanoflavus. 



Method of extraction: Extracted from broth-fil- 

 trate at neutral or alkaline pH with chloroform, 

 methylene chloride, or tetrachloroethane. Back- 

 extracted into acidic water. Mycelium extracted 



two or three times with 0.1 A' HCl, then back- 

 extracted into chloroform at pH 8.5. Process re- 

 peated several times. Final acidic water extract 

 neutralized and cooled to precipitate cyanomycin. 

 Recrystallized from hot water. 



Chemical and physical properties: Monoacidic 

 base. Possibly contains a cjuinone group. Dark 

 blue needles; m.p. r28°C (decomposition). Soluble 

 in water to 0.5 mg per ml; in hot water to 5 mg per 

 ml. Sokdile in lower alcohols, acetone, chloroform, 

 and methylene chloride. Slightly soluble in carbon 

 tetrachloride, ethyl acetate, benzene, and ether. 

 Insoluble in petroleum ether and cyclohexane. De- 

 composes in 0.1 A^ NaOH, but not in 0.1 N HCl. 

 pK = 4.98. Ultraviolet absorption spectrum max- 

 ima at 240 (£;'iL 550), 278 {E\"L 2140), and 384 m/x 

 (E^,n 780) in 0.1 N HCl; at 239 (^IL 760), 278 

 (£lL 1180), 310 {E'-^L 730), and 384 m/x (j5;1L 500) 

 in phosphate buffer at pH 5.0; at 238 (E'Icm 1010), 

 310 (£"1™, 1470), and 378 m,x (ETc^u 320) in carbonate 

 buffer at pH 9.0; at 239, 293, and 370 m^ in 0.1 .V 

 NaOH. Infrared spectrum given in reference 1. 

 Negative Fehling, biuret, ninhydrin, and FeCls 

 tests. Red solution in H2SO4 changes to green- 

 yellow with zinc powder; effect reversilile l\v H2O2 

 but not by bubbling air through the solution. 

 Aciueous solution changed to light blue with zinc 

 powder; change unaffected by atmospheric ()■.> ; 

 and l^ecomes colorless on addition of H2O2 . 

 Weakly alkaline solution reversibly changed to 

 light blue-green with H2O2 . Aqueous solution be- 

 comes yellow-l^rown with H2O2 ; and blue, then 

 colorless with zinc powder. Aciueous solution be- 

 comes yellow-brown on addition of NaHS()4 , 

 then red with H2O2 . C1.5H12N2O2 : C = 69.22%; 

 H = 5.16' f ; N = 10.769f . Picrate: Purple-red nee- 

 dles; m.p. 157.5°C. 



Biological activity: Active on E. coli at 4 ^g per 

 ml and Staph, aureus at 6 Mg per ml. Much less 

 active (10 to 00 fig per ml) on other bacteria tested. 

 Not active on fungi or yeasts. 



Toxicity: Mice tolerate 25 mg per kg intrave- 

 nously. 



Reference: 1. Funaki, M. et al . J. Antibiotics 

 (.lapan) UA: 143-149, 1958. 



C> cloliexiniide 



Produced by: Streptomyces griseus (1, 20, 77) 

 (also produces streptomycin or streptovitacin), 

 Streptomyces sp. related to S. virido- or olivochro- 

 mogenes (52), 5. nonrsei (53) (also produces nysta- 

 tin), Streptomyces sp. differing from S. griseus (71) 

 (also produces a stereoisomer of cycloheximide, 

 "naramycin B"), Streptomyces sp. (41), and iS. 

 albulus (culture produces (72) two forms of cyclo- 



