DESCRIPTIONS OF ANTIBIOTICS 



343 



at 208 (^Icm 1120) (3) and 245 m^ (£'lcm fi72) and 

 a shoulder at 265 to 270 m/x (^IL -130). Infrared 

 spectriun given in reference 2. Prisms: C = 66.63%; 

 H = 6.30%; N = 3.66%. Needles: C = 66.87%; 

 H = 6.61%;N = 3.80%. No S or halogens. Negative 

 FeCl.i , Fehling, ToUen, 2,4r-dinitrophenylhydra- 

 zine, and sodium nitroprusside tests. Purple 

 color in alkaline solution with an absorption 

 maximum at 525 niyu. Yellow in dilute HCl solution 

 with an absorption maximvmi at 430 m^l. "A"- 

 tartrate is an orange crystalline powder. On paper 

 chromatography (paper pretreated with 0.1 A' 

 (pH 3.2) tartrate buffer and developed with water- 

 saturated ethyl acetate), Rf = 0.05. Powder 

 stable. Less stable in acid than in neutral or 

 slightly alkaline solution (2). Diffuses slowly in 

 agar (1). Pluramycin B: Not completely purified. 

 Reddish brown powder. Soluble in methanol, 

 ethanol, acetone, ethyl acetate, butyl acetate, 

 ether, benzene, chloroform, and ethyl Cellosolve. 

 Insoluble in water and petroleum ether. Differs 

 from A in not being transferred into an aqueous 

 phase from ethyl acetate at pH 5.3. Purple color 

 in alkali. Rf = 0.95 in the system described under 

 A. 



Biological actiriti/: Pure pluramycin A inhibits 

 Staph, aureus at 0.02 to 0.1 Mg per ml (2). Crude 

 powder containing both A and B is also active on 

 other gram-positive bacteria. Very slight to no 

 activitj' on gram-negative bacteria, yeasts, and 

 filamentous fimgi (1). Inhibits growth of both 

 solid and ascitic forms of Ehrlich carcinoma in 

 mice (2). 



Toxicity: Pluramycin A: LDso (mice) 25 mg per 

 kg subcutaneously, 6.25 to 12.5 mg per kg intra- 

 peritoneally, and 1.25 to 2.5 mg per kg intrave- 

 nously. Pluramycin A tartrate is more toxic than 

 the free base (4). Causes desquamation and has 

 an antimitotic effect on HeLa cells at 0.06 to 0.15 

 fjig per ml; this activity parallels antitumor ac- 

 tivity in vivo (2). Contact tests using a crude 

 preparation (A and B) destroy the inoculability of 

 Ehrlich carcinoma cells (1). Active on this tumor 

 in mice. Also active on the solid and ascitic forms 

 of sarcoma 180 (mice). Much less active on Yo- 

 shida rat sarcoma (3, 5). 



References: 



1. Takeuchi, T. et al. J. Antibiotics (Japan) 



9A: 22-30, 1956. 



2. Maeda, K. e^aL J. Antibiotics (Japan) 9A: 



75-81, 1956. 



3. Umezawa, H. Giorn. microbiol. 2: 160-193, 



1956. 



4. Takeuchi, T. et al. J. Antibiotics (Japan) 



lOA: 143-152, 1957. 



5. Nishibori, A. J. Antibiotics (Japan) lOA: 

 213-218, 1957. 



Primycin 



Produced by: Strcpto)nyces sp. (1). 



Method of extraction: Acidification of broth- 

 filtrate gives precipitate on which antibiotic is 

 adsorbed. Residue treated with ether, then ex- 

 tracted with methanol. Purification by treatment 

 with colloidal Al (OH) 3 and precipitation on addi- 

 tion of ether, or extraction of a 20 per cent meth- 

 anol solution with butanol and precipitation on 

 addition of ether. Crystallized from methanol- 

 butanol (1 ) . 



Chemical and physical properties: White micro- 

 crystals; m. p. 166-168°C (decomposition). Soluble 

 in methanol ; less soluble in higher alcohols; 

 sparingly soluble in pyridine, glacial acetic acid, 

 and water; insoluble in other solvents. Aqueous 

 solution sensitive to electrolytes. Thermostable. 

 Strongly surface-active. H2SO4 solution first yel- 

 low then red. Negative Fehling, Elson-Morgan, 

 and maltol tests. No reaction with aldehyde re- 

 agents. Positive Brunner-Pettenkoffer and Saka- 

 guchi reactions. Inactivation by acetylation in 

 pyridine reversed by splitting of the acetyl 

 groups. C19H37O7N : C = 58.79%; H = 9.56%; N = 

 3.63% (Dumas). No unsaturation and probably 

 no guanidino group (1, 2, 4). 



Biological activity: Active on gram-positive 

 bacteria, including Staph, aureus at 0.02 to 0.06 

 /ig per ml, and mycobacteria. Virucidal. Partly 

 inactivated by serum. Most active at alkaline pH, 

 pH 7.6 to 7.8 being optimal. 



Toxicity: LDioo (mice) 2.5 mg per kg (no route 

 given). Nontoxic to tissue cultures, and nontoxic 

 to human beings at therapeutic levels (1,2). 



Utilization: Topical application (3). Reputedl}^ 

 active on tubercular infections resistant to other 

 antibiotics (2). 



References: 



1. Vdlyi-Nagy, T. et al. Nature, London 



174: 1105-1106, 1954. 



2. Szil^gyi, I. and Szabo, I. Arzneimittel- 



Forsch. 8: 333-336, 1958. 



3. Molnar, G. and Biro, L. Magyar Voor. 



Lapja 21: 155-159, 1958. 



4. Vdlyi-Nagy, T. and Kelentey, B. Abstr. 



Communs. Symposium on Antibiotics, 

 Prague 47-49, 1959. 



Proactinoniycins 



Produced by: Streptontyces (Proactinomyces) 

 gardneri (1 , 2). 



Synonyms: Proactinomycin B is similnr or 



