202 



DESCRIPTIONS OF ANTIBIOTICS 



tion spectrum maxima (methanol) at 220 to 230 

 m/i (^Ic'm 655) and 275 m^ (Elcm 200). Infrared ab- 

 sorption spectrum given in reference 1. [al^ = 

 — 207° (c = 0.5 per cent in methanol). Positive 

 FeClg (green), neutral permanganate, Br2in CCh , 

 Tollen, 2,4-dinitrophenylhydrazine, and copper 

 acetate tests. Negative Fehling, Molisch, Millon, 

 and ninhydrin tests. C35H42N4O9 or C2.5H31N3O6 : 

 C = 03.7%; H = 6.48%; N = 8.61%. Molecular 

 weight, 525. PA II4B: Weakly acidic polypeptide. 

 Colorless tablets (from methanol) orneedles (from 

 toluene); m.p. 265°C (decomposition). Ultraviolet 

 absorption maxima (methanol) at 260 m/u (Eicm 

 217) and 305 m^ (£l?„> 105). [«]„' = -59.7° (c = 

 0.5 per cent in methanol). Infrared absorption 

 given in reference 1. Positive FeCU (red), neutral 

 permanganate, Bro in CCI4 tests. Negative Tollen, 

 2,4-dinitrophenylhydrazine, copper acetate, Feh- 

 ling, Molisch, Millon, and ninhydrin tests. CjoHes- 

 N,0,2 : C = 62.02%; H = 6.21%; N = 12.77%. 

 Molecular weight, 981. PA lUB-3: Polypeptide 

 differing slightly in amino acid content from PA 

 114B. Needles; m.p. 207-208°C. [«]" = -37.2°. 

 Ultraviolet absorption spectrum maxima (meth- 

 anol) 258 niM (Elcm 204.5) and 305 m^ (^11 95). 

 C = 62.77%o; H = 6.52%o; N = 12.61% (1, 2, 4). 



Biological activity: PA 114A and 114B have a 

 synergistic action. PA 114B-3 and 114 A have a 

 marked synergistic action in vitro. PA 114 B-3 

 and 114B have a similar, but less marked syner- 

 gistic activity. Complex is active on gram-positive 

 bacteria, mycobacteria, and the genera Neisseria 

 and Hemophilus, but not against other gram- 

 negative bacteria. Not active on fungi. Some cross- 

 resistance with carbomycin and erythromycin, 

 but not other commonly used antibiotics. Very 

 slightly active (250 Mg per ml) on Endamoeba histo- 

 lytica. Resistance develops slowly and follows the 

 penicillin ])attern. In vitro activity not reduced 

 by NaCl, glucose, cysteine, thioglycoUate, urea, 

 or serum. Artificial mixtures of A and B are ac- 

 tive over a wide ratio of concentrations within the 

 limits of 20 to 80 per cent. Active in vivo on infec- 

 tions caused by Staph, aureus and Streptococcus 

 pyofjenes (mice). Somewhat active in ovo and in 

 mice on Rickettsia akari and the psittacosis organ- 

 ism. Alone, neither A nor B is active in vivo. Maxi- 

 mal protection with artificial mixtures is obtained 

 with the following combinations: PA 114A 80 to 

 95 per cent; PA 114B 5 to 20 per cent (1,2, 4). This 

 differs from E 129 complex. 



Toxicity: Mice tolerate 200 to 400 mg per kg 

 orally and subcutaneously. Rabbits tolerate at 

 least 100 mg i)er kg intramuscularly' (1, 2). 



References: 



1. Celmer, W. D. ci a/. Antibiotics Ann. 437- 



452, 1955-1956. 



2. Sobin, B. A. et al. U. S. Patent 2,787,580, 



April 2, 1957. 



3. Ball, S. et al. Biochem. J. 68: 24P, 1958. 



4. Hobbs, 1). C. and Celmer, W. D. Federation 



Proc. 18: 246, 1959. 



Antibiotic PA 128 



Produced by: Streptomyces sp. 



Method of extraction: Broth and mycelium ex- 

 tracted with n-butanol at pH 7.0 to 8.0. Clarified 

 extracts concentrated under reduced pressure with 

 addition of water. Purification of residue by coun- 

 tercurrent distribution (ligroin, b.p. 60-90°C, and 

 80 per cent aqueous methanol). Active fractions 

 concentrated to remove methanol, then extracted 

 with ether. Concentration of ether-extracts gives 

 crude substance. Recrystallization from ether. 



Chemical and physical properties: Light yellow 

 rectangular plates; m.p. 143-144°C (decompo.si- 

 tion). Slightly soluble in water. Soluble in lower 

 alcohols, acetone, ethyl acetate, and chloroform. 

 Ultraviolet absorption maxima at 245 m^ (-E'lem 

 468) and 285 m/i (E\l'm 234). Infrared spectrum 

 given in reference 1. [a]f = —2.0° (c = 1 per cent 

 in methanol). Positive 2,4-dinitrophenylhydra- 

 zine, bromine water, and KMn04 tests. Negative 

 FeCls test. No color with aqueous NaOH or 

 H2SO4 . 



Biological activity: Active in vitro on Tricho- 

 monas vaginalis and Endamoeba histolytica. Not 

 active on gram-positive or gram-negative bac- 

 teria or fungi. No activity in vivo. 



Toxicity: Very toxic; 25 mg per kg daily for 5 

 days is lethal to mice. 



Utilization: Possible utilization in studies in 

 vitro on protozoal metabolism. 



Reference: 1. Rao, K. V. and Lynch, J. E. Anti- 

 biotics & Chemotherapy 8: 437-440, 1958. 



Antibiotic PA 132 



Produced by: Streptomyces sp. 



Method of extraction: Broth, acidified to pH 2.5 

 with dilute H2SO4 , extracted with an organic 

 solvent such as chloroform, ether, or methyl iso- 

 butyl ether. Extract concentrated in vacuo. Con- 

 centrate chromatographed on acid-washed alu- 

 mina and developed with chloroform followed by 

 2.5 per cent methanol in CCI4 . Also purified l^y 

 countercurrent distribution (toluene -methanol - 

 water). Ether solution treated dropwise with 

 benzylamine with stirring. Yellow precipitate tri- 

 turated witli ethyl acetate-ether (1:9) to yield 



