DESCRIPTIONS OF ANTIBIOTICS 



337 



on ahunina. Developed with 80 per cent acidic 

 ethanol (pH 3.0). Eluate.s concentrated and ly- 

 ophilized (1). 



Chemical and physical properties: Light yellow 

 hygroscopic powder. Soluble in acidic water and 

 methanol. Less soluble in ethanol. Insoluble in 

 acetone, ether, benzene, chloroform, and petroleum 

 ether. Negative FeCU , biuret, Millon, and nin- 

 hydrin tests. Positive Lassaignes test for nitrogen. 

 Reacts with picric acid, Reinecke's salt, and 

 methyl orange. Stable in dry form. In solution 

 most stable at pH 3.0 at 100°C for 5 minutes; 

 irreversibly inactivated at pH 9.0. 



Biological activity: Active on K. pneumoniae 

 at 3.0 fxg per ml. Less, or not active on other bac- 

 teria tested, including E. coli. and Staph, aureus 

 (12 ng per ml), and Mycobacterium smegmatis (50 

 fxg per ml) (1). Also active on Borrelia duttonii, 

 PlasDtodium berghei, and Trypanosoma equiperdum 

 (3). Has a direct killing action on certain phages: 

 coliphages Ti , T,, , and T7 (but not To , T4r , 

 To , or Ts (2)), Eherthella typhosa phage, Sal. 

 paratyphi phage, and Clostridium perfringens 

 phage (3). Somewhat active on S. griseus phage. 

 Active mainly on free phage, but also inhibits 

 certain absorbed phage in the early part of the 

 latent period. Inactivated phage retains ability 

 to be absorbed and kill host cells, but not to mul- 

 tiply (1). Action not affected by increasing tlie 

 number of phage. Inactivation of free phage in- 

 hibited by deoxyribonucleic acid and to a lesser 

 extent by ribonucleic acid (2). Active in tissue 

 culture on Y-SK poliomyelitis virus. Inhibits 

 PR 8 influenza virus but not herpes simplex in 

 eggs (4). Virucidal {in vitro) action on vaccinia 

 (L.N. and Nelis strains) and herpes simplex; 

 destroys rabies virus (Brussels strain) on contact ; 

 partial virucidal action on poliomyelitis (Theiler 

 and Lansing strains). No //; vitro action on lym- 

 phogranuloma or PR 8 influenza virus (3). 



Toxicity: Mice are killed in 72 hours by injec- 

 tions of 3L25 mg per kg intraperitoneally, or 500 

 mg per kg subcutaneously. Intravenous injection 

 of 500 mg per kg causes immediate death (1). 

 Toxic to mice at therapeutic levels. Not toxic to 

 tissue cultures at 20 mg per ml (3, 4). 



References: 



1. Asheshov, I. N. et al. Antil)iotics & Chemo- 



therapy 2: 36()-374, 1952. 



2. Hall, E. A. and Asheshov, I. N. J. Gen. 



Physiol. 37: 217-230, 1953. 



3. Levaditi, C. et al. Rev. inununoi. IT: 



324-338, 1953. 



4. Asheshov, I. N. et al . Antil)iotics & Chemo- 



therapy 4: 380-394, 1954. 



I'liufioiiiycin 



Produced by: Streptojiiyccs sp. resembling <S. 

 griseolus. 



Method of crtraction: Broth adjusted to pH 

 5.0 and filtered. Filtrate adjusted to pH 7.0 and 

 passed through an lonex C cation-exchange resin 

 column. Elution with 80 per cent aqueous acetone 

 containing 0.2 .Y HCl. Active fractions adjusted to 

 pH 7.0, filtered, and readjusted to pH 5.0. Acetone 

 concentrated to dryness under nitrogen. Purifica- 

 tion by chromatograjjliy on alumina from meth- 

 anolic solution developetl with dry methanol, and 

 chromatography on Darco (i-GO plus Dicalite from 

 acidic water. 



Chemical and physical properties: Basic sub- 

 stance. Soluble in water and methanol. Less sol- 

 uble in ethanol and aqueous acetone. Positive 

 ninhydrin test. Negative biuret, xanthoproteic, 

 Sakaguchi, maltol, Moliseh, Millon, Fehling, 

 Hopkins-Cole, ToUen, and FeCL tests. Stable at 

 acid pH. Unstable at neutrality or at alkaline pH. 

 Ultraviolet absorption spectrum shows end- 

 absorption oidy. Reineckate: m.p. 166-170°C 

 (decomposition). C = 12.38%; H = 0.79%; N = 

 12.14%; S = 14.34%; Cr = 5.24% (sic). 



Biidogicdl activity: Not active on bacteria, fungi, 

 or protozoa. Active on some bacteriophages, 

 including coliphages Ti , T3 , T.=, , and T7 , but 

 not To and Tg or micrococcus phage. Active on 

 Sal. cnteritidis, S. paratyphi B, and Shigella 

 ftcvncri phages. Antiphage activity against free, 

 l)ut not adsorbed phage. 



Toxicity: Mice tolerate al)out (id mg per kg 

 intraperitoneally 



Reference: 1. Mivua. M. .]. Antil)iotics (Japan) 

 9A: 108-112. 195C>. 



IMiafioslalin 



Produced by: Streptom yccs sp. resembling iS. 

 bikiniensis. 



Method of extraction: Ninety per cent of the anti- 

 biotic is present in the mycelium and is extracted 

 with 80 per cent aqueous acetone. Broth extracted 

 with butanol. Acetone-extract concentrated in 

 vacuo to an aqueous residue. Residue extracted 

 with l)utanol, this extract combined with the 

 butanol-extract from the broth, and both extracts 

 concentrated in vacuo following the addition of 

 water. Watery residue extracted with chloroform. 

 Extract concentrated to dryness. Purification by 

 recrystallization from 50 to 60 per cent aciueous 

 acetone, or chromatography on alumina from 

 chloroform-20 per cent ether, developed with 

 chloroform, ethyl acetate, and acetone, and eluted 

 with acetone. The antibiotic is precipitated from 



