352 



DESCRIPTIONS OF AXTIIilOTICS 



centrated HCl, orange color changes to violet on 

 heating. Negative ninhydrin, biuret, Sakaguchi, 

 and Millon tests. Rf values on paper chromatog- 

 raphy given in reference 3. Stable at room tem- 

 perature between pH 2.0 and 10.0. Destroyed by 

 heating at 100°C for 20 minutes at pH above 7.0, 

 but stable between pH 2.0 and 6.0 (1). CssHsn- 

 NsOu : C = 57.3%; H = 4.25%; N = 6.07%. No 

 S or halogens. Acid hydrolysate contains no nin- 

 hydrin-positive substances. Ractinomycin B: Red- 

 dish orange needle-shaped crystals; m.p. 172- 

 175°C (decomposition). Same solubility properties 

 as A, but, as a rule, less soluble. Insoluble in con- 

 centrated HCl and 10 per cent NaOH. XS^',^ 250 

 (£;1L 1080) and 400 to 450 {E\'L 260). FeCU test 

 negative. Other tests and stability as for ractino- 

 mycin A. Contains no halogen or S (1, 3). 



Biological activity: Ractinomycins A and B are 

 active in vitro against gram-positive bacteria and 

 fungi. A is more active than B against gram-posi- 

 tive bacteria but less active against mycobacteria 

 and fungi. B also has a small amount of activity 

 (50 to 100 ng per ml) against gram-negative bac- 

 teria. Both ractinomycins are active against Toxo- 

 plasma gondii (1). A has antitumor activity 

 against the ascitic form of Ehrlich carcinoma, and 

 causes the disappearance of HeLa cells in mitosis 

 at 25 mg per ml (2, 3). 



Toxicity: Ractinomycin A: LDjo (mice) 10 mg 

 per kg intraperitoneally (1), 5 to 12.5 mg per kg 

 intravenously (3). Ractinomycin B: Mice tolerate 

 25 mg per kg intraperitoneally (1 ) . 



References: 



1. Utahara, R. ct al. .1. Antibiotics (Japan) 



8A: 132-135, 1955. 



2. Umezawa, H. (!iorn. microbiol. 2: 160- 



193, 1956. 



3. Utahara, R. J. Antii)i()tics (.)ai)an) lOA: 



115-119, 1957. 



Raisn<>iii> fin 



Produced by: Sireptoitiyces l^en(u(■k■ensis (1). 



Method of extraction: Broth adjusted to pH 2.5 

 and filtered. Filtrate adjusted to pH 9 and ex- 

 tracted with n-butanol. Butanol evaporated to 

 dryness. Residue taken up in 0.1 A" HCl and evap- 

 orated to dryness. 



Chemical and physical properties: Dark yellow 

 basic substance. Insoluble in water, acetone, and 

 ether. Soluble in ethanol, methanol, butanol, and 

 isopropanol. Hydrochloride and sulfate slightly 

 soluble in water. No end-absorption in ultraviolet 

 light. 



Biological activity: Moderately active on gram- 

 positive and gram-negative bacteria, but not on 



A', pneumoniae, Ps. aeruginosa, mycobacteria, or 

 yeasts. 



Toxicity: LDoo (rats) 28 to 35 mg per kg (route 

 not given). 



Reference: 1. Barr, F. S. and Carman, P. E. 

 Antil)iotics & Chemotherapy 6: 286-289, 1956. 



Raninacin 



Produced by: Streptomyces ramnaii (2). 



Method of extraction: Extraction of culture-fil- 

 trate with ether at pH 8.0. Extraction of the 

 mycelium with ethanol; evaporation of ethanol to 

 dryness. Residue suspended in water at pH 8.0; 

 extraction with ether. The two ether-extracts 

 combined and evaporated to dryness. The residue 

 suspended in chloroform and chromatographed on 

 activated alumina. The active material moves 

 almost with the solvent front. Crystallization 

 from a petroleum ether-alcohol mixture. 



Chemical and physical properties: Stable sub- 

 stance (can be autoclaved at 15 pounds per sciuare 

 inch for 20 minutes at pH 2 to 10); m.p. 235°C. 

 Tentative empirical formula: C26H43OS . Sparingly 

 soluble in water. Very soluble in alcohol, acetic 

 acid, ethyl acetate, chloroform, and ether. Mod- 

 erately soluble in benzene and petroleum ether. 

 Does not decolorize bromine in carbon tetrachlo- 

 ride. Positive test for benzenoid structure. Paper 

 chromatography (n-butanol-acetic acid-water, 

 4:1:5) and countercurrent distribution of 19 trans- 

 fers (petroleum ether, h.p. 80-90°C, 95 per cent 

 ethanol and water, 4:3:1) reveal only one active 

 component. (1). 



Biological activity: Active ;'/( vitro against gram- 

 positive bacteria and one strain of Pr. vulgaris. 

 No activity against one strain of Ps. aeruginosa. 

 Active against two fungi out of nine tested. 



References: 



1. Ahmad, K. and Islam, M. F. Nature, 



London 176: 646-647, 1955. 



2. Ahmad, K. cl al. Ann. Biochem. and lilxptl. 



Med. (Calcutta) 15: 175-180, 1955. 



Raroniycin 



Produced by: Streptomyces albochromogenes, 

 closely related to S. griseochromogenes (blast i- 

 cidin-producer) (3). 



Method of extraction: Mycelium extractetl with 

 60 to 80 per cent acetone. Extract concentrated 

 and extracted with tnitanol. Broth-filtrate ex- 

 tracted with butanol. Active substance precii)i- 

 tated on addition of ether (2). 



Chemical and physiccd properties: m.p. 211- 

 213°C. Soluble in alkaline water, methanol, eth- 

 anol, atiueous butanol, aqueous acetone, diox- 



