320 



DESCRIPTIONS OF ANTIBIOTICS 



i\ocar<l<>rii!)iii 



Produced by: Xocardia narashinoensis (2). 



Method of extraction: Extraction of the broth- 

 till rate with n-butanol at pH 2.0 to 3.0. Concentra- 

 tion of the solvent layer to syrup in vacuo. Syrup 

 extracted with acetone; again concentrated to 

 syrup. Extraction of the syrup with water; 10 per 

 cent NaOH added dropwise until a deep red pre- 

 cipitate forms. Precipitate collected by centrifu- 

 gation, washed with water, and dried. Nocardoru- 

 bin can also be extracted with acetone from the 

 mycelium. 



Chemical and physical properties: Red at alkaline 

 reaction, yellow at acid pH. Alkaline form is 

 slightly soluble in dioxane, ethyl acetate, chloro- 

 form, and propylene glycol. It is almost insoluble 

 in most organic solvents and water. The acid form 

 is soluble in water and organic solvents. Carbo- 

 hydrate and protein tests negative. Turns black 

 at 180°C, but does not melt at 250°C. Aqueous 

 solutions stable for at least 2 months at 27°C. 

 Heating solutions at pH 2.0 reduces the activity 

 in 5 to 15 minutes at 60°C. At pH values above 

 5.8, this treatment does not destroy the antibiotic 

 activity. 



Biological activity: Active against many gram- 

 positive bacteria in a concentration of 0.001 to 

 5.0 fig per ml. Also active against mycobacteria 

 and actinomycetes. Active against certain gram- 

 negative bacteria at a concentration of 20 fig per 

 ml. Activity against fungi low or ml. Limited 

 activity against D. pneumoniae in mice. The de- 

 velopment of resistance to nocardorul)in is slow. 



Toxicity: LDo (mice) about 154 mg per kg; LDmn 

 about 230 mg per kg intraperitoneally. 



References : 



1. Aiso, K. et al. J. Antibiotics (Japan) "A: 



1-6, 1954. 



2. Endo, T. J. Antibiotics (Japan) 9A: 228, 



1956. 



Noforiiiicin 



Produced by: Nocardia formica. 



Synonym: Antibiotic MK 61. 



Method of extraction: Adsorption from the cul- 

 ture-filtrate on activated carbon, and elution with 

 90 per cent acpieous methanol under acidic condi- 

 tions. Concentration by chromatography over 

 activated carbon or a cation exchange resin. The 

 salt-free concentrate evaporated until crystals 

 form (1). 



Chemical and physical properties: Basic sub- 

 stance. Analysis of crystalline sulfate: CnH,'j4Nifi 

 Oo(S04)2; m.p. 265°C (decomposition) for the 

 hydrochloride. Water-solul)le. Dialyzable (1). 



Stable in solutions up to pH 8.0. Among the hy- 

 drolysis products, ammonia and glutamic acid 

 have l)een identified. Nonreducing. No phenolic 

 groups (1). 



Biological activity: Prolongs life of mice infected 

 with swine influenza, influenza A (PR 8), or in- 

 fluenza B (Lee). Treatment is effective whether 

 the material is administered subcutaneously, 

 intravenously, or orally. An effect is obtained 

 when the material is administered as early as 24 

 hours before, or as late as 24 hours after infection. 

 Best results obtained by treating the mice with 

 multiple small doses for 3 days following infection. 

 The agent is also active against mumps and 

 against Newcastle disease virus (NDV) in em- 

 bryonated eggs. No activity demonstrated against 

 NDV infection in mice or against the nontrans- 

 missible pneumonia produced by NDV in mice. 

 No activity against SK encephalomyelitis in mice, 

 hog cholera in pigs, enteritis in mink, or hepatitis 

 in dogs (1). Active on virus development in host 

 cell, not on free virus. Inhibits the production of 

 tobacco mosaic virus in leaf discs floated in solu- 

 tions of the antibiotic. Active in rn'o against south- 

 ern bean mosaic virus and tobacco mosaic virus in 

 intact plants (2, 3). 



Toxicity: Mice tolerate daily doses of 5 mg per 

 kg subcutaneously and intravenously; 12.5 mg per 

 kg tolerated orally (1). 



References : 



1. Harris, 1). A. et al. Antibiotics Ann. 1953- 



1954, p. ()09-621. 



2. Schlegel, D. E. and Rawlins, T. E. Phyto- 



pathology 44:328-329,1954. 



3. Gray, R. A. Phytopathology 45: 281-285, 



1955. 



Novobiocin 



Produced hi/: Streptouiyces spheroides (2, 7), S. 

 niveus (3, 11), S. griseoflavus (also produces an 

 actinomycin (1, 30)), S. griseus (61), and Strep- 

 tomyces sp. (22). 



Synonyms: Cathomycin, streptonivicin, cardel- 

 mycin, antibiotic PA 93, crystallinic acid, vulca- 

 mycin (Italy), gri.seoflavin, albamycin, biotexin, 

 inamycin, cathocin, antibiotic S 800. 



Remarks: Novobiocin was reported to have 

 been isolated in 1953 by Waga under the name 

 griseoflavin. Waga's original description (1) leaves 

 this open to some doubt, since unfortunately he 

 published no ultraviolet or infrared spectrum, al- 

 though Kuroya (3) clearly isolated novobiocin 

 from Waga's culture 5 years later. The principal 

 discrepancies between Waga's original description 

 (apparently he isolated the sodium salt of novo- 



