DESCRIPTIONS OF ANTIBIOTICS 



165 



at 130°C and resolidifies at 145°C. Sohible in water 

 and soluble in lower alcohols and acetone while 

 warm. Slightly soluble in ethyl acetate, [a]^ = 

 +58° (c = 1 per cent in water). Acetylation of the 

 acetate or free base with acetic anhydride gives a 

 l)iologically inactive N-acetyl derivative: white 

 needles; m.p. 254-255°C; plvl = 8.4 (2). 



Biological activity: Moderately active on gram- 

 positive and gram-negative bacteria. Resistance 

 develops easily. No cross-resistance with other 

 common antibiotics (1). Protects mice from in- 

 fections with Staph, aureus and K. pneumoniae at 

 high doses. No effect on infections with D. pneu- 

 uLoniae, Pr. vulgaris, Sal. typhimurium, or M. 

 tuberculosis. Very slightly active against Plas- 

 modium lophurae, (chicks) but not Sckistosomci 

 uiansoni (mice), helminths (rat), or protozoa (1). 

 Protects X-ray irradiated rats against the trans- 

 plantable human neoplasms H.S. No. 1 sarcoma 

 and H. ep. No. 3 carcinoma when given 24 hours 

 after tumor implantation. Ineffective against 

 these tumors after they were established (4 days 

 post-implantation) (4). Not effective against H.ep. 

 No. 3 in mice, hamsters, or eggs (3). Active on 

 sarcoma 180 (ascites) , Ehrlich carcinoma (ascites) , 

 carcinoma 1025, glioma 2(5, Walter carcinosarcoma 

 256, and slightly active on adenocarcinoma E()771 

 (5). Active on a large number of transplanted 

 mouse leukemias, including lines resistant toother 

 antitumor agents (6). 



Toxicity: LD50 (mice) 800 ± 27 mg per kg and 

 1550 ± 26 mg per kg (rat) intravenously (1). 



References: 



1. Pittillo, R. F. ('/ at. Antil)iotics Ann. 497- 



504, 1958-1959. 



2. Haskell, T. H. and Bartz, Q. R. Antibiotics 



Ann. 505-509, 1958-1959. 



3. Merker, P. C. and WooUey, (i. W. Anti- 



biotics Ann. 515-517, 1958-1959. 



4. Teller, M. N. et at. Antibiotics Ann. 518- 



521, 1958-1959. 



5. Sugiura, K. and Reilly, H. C. Antibiotics 



Ann. 522-527, 1958-1959. 



6. Burchenal, J. H. et al. Antibiotics Ann. 



528-532, 1958-1959. 



Actinoflocin 



Produced by: Streptouiyces sp. resembling <S. 

 albus (3). This cvilture also produces si.x other 

 antibiotics (3, 4). 



Synonym: Kikuchi's third substance (1). 



Method of extraction: I. Broth extracted with 

 chloroform at acid pH. Chromatography of con- 

 centrated extract on celhdose powder. Washed 

 with 20 per cent NH4CI and eluted with water (3, 



4). II. Broth adsorbed on IRC-50 (H+ phase) at 

 pH 7.8 and eluted with 80 per cent acetone. Eluate 

 extracted with chloroform at pH 5.0 (4). 



Chemical and physical properties: Soluble in most 

 organic solvents. Sparingly soluble in water. 

 Ultraviolet absorption spectrum maxima at 231 

 and 276 m/x. Stable in solution from pH 2.0 to 8.0. 

 Thermostable (2). 



Biological activity: Active on Streptococcus 

 hemolyticus at 1.56 )ug per ml (2). Slightly active on 

 B. subtilis. Not active on Sarcina lutea, C. albicans 

 or A. niger (4). Slight activity on ascitic and solid 

 forms of Ehrlich carcinoma and sarcoma 180 (2). 



Toxicity: LD50 (mice) 3 mg per kg intraperi- 

 toneally (2). 



References: 



1. Kikuchi, K. J. Antibiotics (Japan) 8A:145- 



147, 1955. 



2. Katagiri, K. et al. Chemotherapy (Tokyo) 



4: 143, 1956. 



3. Sato, K. and Katagiri, K. Chemotherapy 



(Tokyo) 5: 182-183, 1957. 



4. Katagiri, K. el al. Shionogi Kenkyusho 



Nempo 7: 715-723, 1957. 



Actiiioidiii 



Produced by: Nocardia (Proactinouiyces) acti- 

 noides. 



Method of extraction: Atlsorption on activated 

 carbon. Elution with 80 jjer cent aqueous acetone 

 at pH 3.0. Purification by chromatography on 

 "Permutit" (alumina-sodium silicate). Washed 

 with distilled water and eluted with 5 per cent 

 NaCl solution. Salt conversion: picrate to hydro- 

 chloride. Reprecipitation from methanol with ace- 

 tone. Also forms a reineckate. Carboxylic cation 

 exchange resins (H+ form) can also be used to 

 purify actinoidin. 



Chemical and physical properties: Basic polypep- 

 tide. HCl salt: water-soluble, white amorphous 

 powder. Free base: Little solubility in water except 

 at pH 8.5. Slightly soluble in methanol and ethanol. 

 Insoluble in butanol, acetone, ether, and other 

 nonpolar solvents. Most stable at acid or neutral 

 pH. N = 7 per cent (Kjeldahl); amino N = 2 per 

 cent (Van Slyke). Positive Pauly, Molisch, and 

 biuret reactions. Product of diazotization reacts 

 with a-naphthol to give a brownish green color. 

 Negative orcin, FeCls , Fehling, Seliwanoff tests, 

 and negative test for amino sugars. Fehling reac- 

 tion becomes positive after 3 to 5 minutes of heat- 

 ing in 5 per cent HCl. Mild acid hydrolysis yields 

 two fractions: 1 = 5 per cent HCl -insoluble; II = 

 5 per cent HCl-soluble. Fraction I contains many 



