DESCRIPTIONS OF ANTIBIOTICS 



353 



ane. and pyridine. Slightly sohihlc in acetone 

 butanol, and isopropyl alcohol. Insoluble in acidic 

 water, benzene, ether, petroleum ether, hexane, 

 carbon tetrachloride, ethyl and l)utyl acetate. No 

 characteristic maxima in ultraviolet light-absorp- 

 tion spectrum. Infrared spectrum indicates a 

 carboxyl group. Titration and solubility indicates 

 the presence of an acidic group. Contains acetyl- 

 able hydroxy! groups, [af,," = +22°, C = 57.97%; 

 H = 8'46%;"n = 0.44% (3). 



Biological activity: Antitumor activity on ascites 

 and solid forms of Ehrlich carcinoma and Crocker 

 sarcoma 180 in mice and Yoshida sarcoma (ascitic) 

 in rats. Retards mitosis of HeLa cells at 15 to 125 

 fxg per ml and causes degeneration at 250 ;ug per 

 ml (2). Not active on microorganisms (3). 



Toxicity: Mice tolerate 200 mg per kg intrave- 

 nously, and 1 gm per kg intraperitoneally (1). 



References: 



1. Tanaka, N. et al. J. Antibiotics (Japan) 



lOA: 189-194, 1957. 



2. Tanaka, N. et al. Gann 48:445-447, 1957. 



3. Tanaka, N. et al. J. Gen. Appl. Microbiol. 



4: 259-271, 1958. 



Resistoniyciii 



I'liiilucrd by: Strains of Streptontyces rcsisto- 

 inycijivus (2j and variants thereof (3), and S. 

 arabicus (4). 



Synonym: Croceomycin (4). 



Method of e.ctrartion: Dried powtlered mycelium 

 treated with petroleum ether, then extracted with 

 ether. Antibiotic crystallized from boiling ether, 

 and from ether concentrate. Chromatographed on 

 calcium sulfate from dioxane-ether (1:10). Crys- 

 tallized from acetone or dioxane (3). 



Chemical and physical properties: Weakly acidic 

 substance. Yellow needles; m.p. 315°C (decom- 

 position). Becomes orange at 300°C and also when 

 tjoiled in a solvent of high boiling point . Sublimes 

 in nicuo at 213-215°C. Scarcely soluble in water 

 and in organic solvents, except for dioxane and 

 tetrahydrofuran. Soluble in concentrated H2SO4 

 to give a yellow solution with green fluorescence. 

 Soluble in alkaline water (red-yellow). Ultraviolet 

 absorption spectrum maxima at about 270, 290, 

 320, 340. and 460 ni/.. C^sHisOe : C = 70.43%; H = 

 4.75%; O = 24.25%; four active H = 1.2%; C— 

 CHs = 4.4%. Very stable to the action of alkali, 

 acid, and heating. Not a ciuinone. Monosodinm 

 salt: Red, water-soluble crystals. Monostearate: 

 Yellow rhomboid crystals. M.p. (not sharj)) 113°C. 

 Soluble in petroleum ether (1, 3). 



Binh)(/ii-(il activity: Active on Staph, aurriis and 



B. sul)lilis at 1 : 20,000,000, and on M. tulxrrulosis 

 at 1:500,000 to 1,000,000 (1). 



Toxicity: LD.50 (croceomycin) 20 mg per kg 

 intraperitoneally (4). 



References: 



1. Brockmann, H. and Schmidt-Kastner, G. 



Naturwissenschaften 38: 479-480, 1951. 



2. Lindenbein, W. Arch. Mikrol)iol. 17: 3(31- 



383, 1952. 



3. Brockmann, H. and Schmidt-Kastner, (J. 



Chem. Ber. 87: 1460-1469. 1954. 



4. Shibata, M. et al. Ann. Rept . Takeda Re- 



search Lab. 16: 82-87, 1957. 



Khodocidiii 



Produced l)y: Streptumyces phoenix. 



Method of extraction: Addition of 0.03 per cent 

 H2O2 to broth. Filtration of the mycelium. Addi- 

 tion of 15 per cent NaCl; extraction with ethyl 

 acetate. Concentration, addition of petroleum 

 ether, extraction with water. Addition of 2 per 

 cent NaHS04 , washing with ethyl acetate. After 

 addition of 2 per cent acetone, extraction with 

 ethyl acetate. Addition of petroleum ether, extrac- 

 tion with water, concentration, lyophilization. 



Chemical and physical properties: Red powder, 

 showing a broad peak of absorption at 500 to 530 

 myu. Soluble in water and in many organic solvents. 

 Inactivated rapidly by dilute acids and alkalies. 

 Inactivated by the mycelium of S. phoenix in 

 absence of excess oxygen. Organic solvent solu- 

 tions and dry jjowders are stal)le indefinitely at 

 5°C. 



Biological activity: Active against mycobacteria, 

 gram-positive and gram-negative bacteria. Active 

 against Streptococcus pyogenes in mice. Much 

 more active by the intraperitoneal route than l)y 

 the intravenous or intramuscular routes. 



'Toxicity: LD.50 (mice) 2.1 mg per kg intraperi- 

 toneally, 2 mg per kg intravenously, and 3 mg per 

 kg intramuscularly. 



Reference: 1. Charney, J. et al. Antibiotics ct 

 Chemotherapy :?: 788-792, 1953. 



Uli(>4l(>iii> cetiii 



Produced l)y: Red mutant of Strcptmnyces 

 griseus. 



Remarks: Originally described as "rhodo- 

 mycin." 



Method of extraction-: Precipitated from broth 

 with acid. Precipitate extracted successively with 

 methanol. Methanol concentrated iti vacuo until 

 precipitate forms. Broth also extracted with 

 n-butanol at ])H 7.2, then at pH 3.0. Extract 

 washed with water, then extracted with 0.2 .1/ 



