DESCRII'TIONS OF ANTIBIOTICS 



293 



tion spectrum given in reference 1. Negative nin- 

 iiydrin, biuret, anthrone, FeCl.t , Elson-Morgan, 

 and Sakaguchi tests. No nitro or oxime groups. 

 Unstable to alkaline pH; more stable at acid pH. 



Biological activity: Active on HeLa cells in tis- 

 sue culture (human cervical carcinoma cell). 



Reference: 1. Sekizawa, Y. J. Biochem. (To- 

 kyo) 4.>: 150 H)2, 1958. 



Leucoinyciii 



Produced by: Streptoniyces kitatiatoensis strains 

 (2, 9) and Streptotnyces sp. (12). 



Synonym: Antibiotic C (537 (12). 



Method of extraction: I. Culture medium acidi- 

 fied, stirred with "Dicarite," and filtered. Filtrate 

 extracted with benzene at pH 7.2 to 9.0. Back- 

 extracted into water at pH 3 to 4. Extracted into 

 ether at pH 9.0. Extract evaporated to dryness. 

 Purified by treating a methanolic solution with 

 activated carbon, then chromatographing on 

 alumina from benzene, developed with acetone- 

 benzene (3:7). Precipitated as the tartrate. Broth 

 contains three components; mycelium, a fourth. 

 The three bases are demonstrable on countercur- 

 rent distribution (isopropyl ether-0.062 M phos- 

 phate buffer pH6.25, 1:1) (5). 



Chemical and physical properties: Basic sub- 

 stances. Complex: Yellowish rhoml)oid crystals; 

 m.p. 126-129°C (1, 5). Soluble in alcohols, acetone, 

 ethyl acetate, butyl acetate, chloroform, ether, 

 and benzene. Slightly soluble in water. Insoluble 

 in petroleum ether. Ultraviolet absorption spec- 

 trum maximiun at 230 to 232 m^i (^lt"m 228) and a 

 weak band at 285 myu (£'i°cm 8.6) (ethanol) (4). In- 

 frared absorption spectrum given in reference 1. 

 [a]'o = —60.42° (c = 2 per cent in ethanol). pKi, = 

 7.5 (water). Positive Molisch, Schiff, Tollen, and 

 Seliwanoff tests. Negative Fehling, Benedict, 

 biuret, ninhydrin, Sakaguchi, glucosamine, xan- 

 thoproteic, FeClij , and maltol tests. Violet color 

 ill concentrated HCl, brown-purple in concen- 

 trated H2SO4 , and yellow in alkaline methanol. 

 Gives a precipitate with trichloroacetic acid (1, 

 4). C33-3sH54-6f,NO„.i.. : C = 61.32%; H = 8.61%; 

 N = 2.03%. Hydrochloride: White, column-shaped 

 crystals. Acetate: Crystalline substance; m.p. 

 135. 5°C. Biologically active. Tartrate: White 

 needles; m.p. 125°C. Very soluble in water, alco- 

 hols, and acetone. Slightly soluble in chloroform 

 and ether. Insoluble in benzene, petroleum ether, 

 dichloroethylene, and trichloroethylene. Aciueous 

 solution loses 28 per cent of its potency at room 

 temperature in 15 days (1). Base 0: m.p. 135°C. 

 C = 60.1%; H = 8.4%; O = 28.0%; N = 1.6%. 

 jiKi, = 7.2. Ultraviolet sj)ectrum maxima at 231 



niM (Ell,, 333) and 279 m/x (^I'cm 5). Rf = 0.03 

 (stationary phase: disodium phosphate; mobile 

 phase: cyclohexane-methyl isobutyl ketone, 

 85:15). Base I: m.p. 142-143°C. [a]f = -76° (c = 

 1 per cent in methanol). C = 60.1%; H = 8.6%; 

 O = 28.5%; N = 1.7%. pK,, = 7.1. Ultraviolet 

 absorption spectrum maxima at 231 niyu (E'll,,, 296) 

 and 279 m^- {Eiln 2.5). Rf = 0.03 (above system). 

 Base II: m.p. 139°C. C = t)0.2%; H = 8.3%; 

 O = 29.1%; N = 1.5%. Ultraviolet absorption 

 spectrum juaxima at 231 mn (ET^,,, 330) and 279 m^t 

 {Ei%n 2.2). Rf = 0.15 (above system) (8). 



Biological activity: Active on gram-positive bac- 

 teria and mycobacteria. Not active on gram-nega- 

 tive bacteria, except the Hemophilus-Neisseria 

 group. Not active on filamentous fungi or yeasts 

 (1). Cross-resistance with oleandomycin but not 

 erythromycin (11, 12). Less active at alkaline 

 than at acid pH. Active in vivo against Staph, 

 aureus, Streptococcus pyogenes, Clostridium welchii 

 (guinea i)ig), Borrelia duttonii (mice), Rickettsia 

 tsutsngamushi (mice), Rickettsia prowazekii (chick 

 embryos), lymphogranuloma (mice), and sheep 

 infectious pneumonia. Moderately active on 

 Treponema pallidum (guinea pigs and rabbits). 

 Not active on Trypanosoma evansi (mice) or rabies 

 virus (mice) (3, 7, 12). Addition to the soil in which 

 a cucumber seedling is growing doubles the curva- 

 ture caused by a one-sided growth of the hypocotyl 

 that occurs when one of the cotyledons is shaded 

 (6). 



Toxicity: LDjo (mice) 650 mg per kg intrave- 

 nously, >800 mg per kg subcutaneously. Mice 

 tolerate >2 gm per kg of the tartrate orally (1). 



Utilization: Effective in a case of chronic chole- 

 cystitis (10). 



References: 



1. Hata, T. et at. J. Antibiotics (Japan) 6A: 



87-89, 1953. 



2. Hata, T. e< rt/. J. Antil)iotics (Jai)an) 6A : 



109-112, 1953. 



3. Hata, T. et al. J. Antil)iotics (Japan) 6.4: 



163-171, 1953. 



4. Sano, Y. et al. J. Antibiotics (Japan) "A: 



88-92, 1954. 



5. Sano, Y. J. .Vntiliiotics (Japan) 7A: 93- 



97, 1954. 



6. Kribben, F. J. Naturwissenschaften 41: 



144-145, 1954. 



7. Hashimoto, T. et al. Japan. J. Bacteriol. 



10: 787-790, 1955. 



8. Despois, R. et al. Giorn. microliiol. 2: 



76-90, 1956. 



9. Nakamura, G. et al . J. Antibiotics (Japan) 



9B: 213-217, 1956. 



