386 



DESCRIPTIONS OF ANTIBIOTICS 



Dicalite column with solvent system isobutanol- 

 cyclohexane-pH 4.0 buffer (20:4:4). The products 

 of the peak fractions again chromatographed on 

 Dicalite, with the solvent system methyl ethyl 

 ketone-cyclohexane-pH 4.0 buffer (9:1:1.43). Ac- 

 tive fractions pooled and distributed for 775 trans- 

 fers between methyl ethyl ketone and water. 

 Active fractions pooled and water removed by 

 distillation. Crystallization from anhydrous 

 methyl ethyl ketone solution. Recrystallization 

 from 95 per cent ethanol (2) . 



Chemical and physical properties: Crystalline 

 product is a mixture of crystals of various types. 

 Very soluble in water; soluble in lower alcohols; 

 relatively insoluble in less polar solvents. Decom- 

 poses with evolution of gas at about 115°C and 

 becomes a clear liquid by 125°C. Tentative em- 

 pirical formula: C14H27N5O12 . Maximal absorption 

 of ethanolic solution at 228 niju, with very weak 

 maxima at 380, 394, and 412 m^- Infrared absorp- 

 tion data given in reference 1. Maximal stability 

 at pH 4.0. No loss of activity of dry samples at 

 room temperature for 30 days and at 4°C for 6 

 months. In 10 per cent aqueous sodium hydroxide, 

 streptozotocin decomposes immediately, with 

 production of the gas diazomethane. Positive 

 Liebermann nitroso test. Negative Benedict, 

 ninhydrin, and biuret tests. After evolution of 

 diazomethane, acidification causes evolution of 

 carbon dioxide. Oxidation of residue with peri- 

 odate gives aldehyde and formic acid. The follow- 

 ing N-nitrosomethylamide function is suggested 

 to exist in streptozotocin (2) : 



O NO 

 R— C— N CH3 



Biological activity: Active against gram-positive 

 and gram-negative bacteria. Little or no action 

 against strains of Ps. aeruginosa, Sh. dysenteriae, 

 K. pneumoniae, Neisseria, Clostridium, and He- 

 mophihis. Bacteria were inculcated for only 8 

 hours before end-points of activity were deter- 

 mined because the antibiotic is not stable in most 

 laboratory media over a 24-hour period. No bac- 

 tericidal activity (3). Development of resistance 

 rapid. No cross-resistance with commonly used 

 antibiotics (4). Active in mice infected with Staph, 

 aureus, Pasteurella mullocida, and Pr. vulgaris 

 when administered subcutaneously or orally (3). 



Toxicity: Mice tolerate 200 mg per kg per day 

 for 14 days orally. 



References: 



1. Vavra, J. J. et al. Antibiotics Ann. 1959- 

 1960, pp. 230-235. 



2. Herr, R. R. et al. Antibiotics Ann. 1959- 



1960, pp. 236-240. 



3. Lewis, C. and Barbiers, A. R. Antil)iotics 



Ann. 1959-1960, pp. 247-254. 



4. Hanka, L. J. and Sokolski, W. T. Antibi- 



otics Ann. 1959-1960, pp. 255-261. 



Sulfaclin 



Produced by: Streptoiuyces sp. resembling S. 

 roseus (1). 



Method of extraction: Broth-filtrate adjusted to 

 pH 7.0 with H2SO4 , and extracted with n-butanol. 

 Extract evaporated in vacuo at 45°C. Residue 

 treated with boiling ether, then extracted with 

 chloroform. Purification by chromatography on 

 Florisil from chloroform, and elution with 10 per 

 cent ethanol in chloroform. Active fractions evap- 

 orated to dryness in vacuo. Crystallized from a 

 chloroform solution by concentration and addi- 

 tion of ethanol; or from boiling ethanol (1). 



Chemical and physical properties: White needles 

 (from ethanol) or double pyramids (from chloro- 

 form); m.p. 245-275°C (decomposition). Very sol- 

 uble in chloroform; soluble in ethanol, ethyl ace- 

 tate, dioxane, and butanol; somewhat soluble in 

 methanol. Positive Fehling (on Ijoiling) test. 

 Negative Sakaguchi, Molisch, biuret, FeCls , and 

 KMn04 tests. Dialyzes with loss of activity. Not 

 destroyed in boiling ethanol. C = 50.28%; H = 

 6.04%i N = 17.21%; S = 14.11%. C,,8H55N„07S4 

 or Co7H4oO,,N8S3 (1). 



Biological activity: Active on certain gram-posi- 

 tive bacteria, and on Neisseria sicca alone of the 

 gram-negative bacteria tested. Not active on 

 mycobacteria. Active on D. pneumoniae infections 

 in mice (2). 



Toxicity: LD50 (mice) 148.5 mg per kg int ra- 

 pe ritoneally. 



References: 



1. Junowicz-Kocholaty, R. et al. J. Biol. 



Chem. 168:765-769,1947. 



2. Morton, H. E. Proc. Soc. Exptl. Biol. Med. 



66: 345-348, 1947. 



Siilfoeidin 



Produced by: Sircplouiyccs sp. 



Method of extraction: Filtered broth is extracted 

 with chloroform; extract concentrated in vacuo 

 and purified by Florisil chromatography (10 per 

 cent ethanol in chloroform, eluant). Active eluates 

 concentrated lo dryness. Methanol-extract of 

 residue filtered and concentrated to dryness. Resi- 

 due extracted with chloroform, and crude sulfo- 

 cidin precipitated by adding petroleum ether with 

 vigorous stirring. Chromatography on carl)on- 



