344 



DESCRIPTIONS OP^ AXTIBIOTICS 



identical to griseomycin, and proactinomycin A 

 is similar or identical to picromycin (3). 



Method of extraction: Broth extracted with amyl 

 acetate at pH 10.0. Extract shaken with acetate 

 buffer at pH 4.0. Acjueous extract adjusted to pH 

 10.0 and re-extracted into amyl acetate. Amyl 

 acetate distilled in vacuo, then extracted three 

 times with water at pH -1. Aqueous extract concen- 

 trated by vacuum distillation and lyophilization. 

 Purified by partition between dilute HCl and bu- 

 tyl alcohol-benzene mixtures on a silica gel col- 

 \min. Count ercurrent distribution (diethyl ether- 

 0.5 .1/ phosphate but!er) indicates the presence of 

 three components. Proactinomycin A is crystal- 

 lized from a concentrated aqueous ether solution, 

 and recrystallized from chloroform on addition of 

 ether. Proactinomycin B is obtained by addition 

 of light petroleum ether to a concentration of an 

 ether solution of active fractions (3). 



Chemical and physical -properties: Complex: 

 Basic substance (3). Slightly soluble in water. 

 Soluble in alcohol, acetone, ether, chloroform, and 

 benzene. Salts: Soluble in water, alcohol, and 

 acetone. Salts are formed with picric, picrolonic, 

 flavianic, reinecke, and helianthic acids (1). Stable 

 in aqueous solution at pH 2 to 8, but inactivated 

 at room temperature at pH >10.0, and by boiling 

 at pH 2. pK = about 9. Alkaline hydrolysis prod- 

 ucts include dimethylamine; a base, CisH-sNOo ; 

 and a neutral substance, C6H9O2 , from which an 

 osazone can be obtained. Proactinomycin A: Short 

 thick plates or short prisms; m.p. 168-ir)9°C. Solu- 

 ble in chloroform, acetone, alcohol, and dilute 

 acid. Slightly soluble in ether and light petroleum 

 ether. Insoluble in water and dilute alkali. Ultra- 

 violet absorption spectrum maximum at about 240 

 ni/i, with an inflection at al)0ut 260 m/.i. C = 63.2%; 

 H = 9.04%; N = 2.67%; X— CH, = 7.35%; 

 C— CH3 = 18.8%; O— CH:, = 1.1%,- Molecular 

 weight, 445. C27H470sN. Proactinomycin B: 

 Doubtfully crystalline; m.p. 83-87°C. Ultraviolet 

 absorption spectrum maxima at about 245 and 270 

 niM. C = 63.8%; H = 9.4%; N = 2.71%; N— CH3 = 

 8.7%; C— CH3 = 18.04%. Molecular weight, 513. 

 C2SH49OSN. Proactinomycin C: Not crystallized. 

 Ultraviolet absorption spectrum maxima at about 

 240 and 295 m/x, with inflections at aliout 280 and 

 310 niM. C = 65.5%; H = 9.2<%; N = 3.08%,; 

 N— CH:i = 8.5%,; C— CH, = 18.6%. Molecular 

 weight, 322. C.:4H4iOfiN (3). 



Biological activity: Complex: Active on gram- 

 positive bacteria. Slightly active on Xcisseria 

 meningitidis and Sal. cnteritidis, l)ut not on Sal. 

 typhosa. Not active on other gram-negative bac- 

 teria or mycobacteria (2). Some activity against 



Streptococcus pyogenes infections in mice. \'ery 

 slightly active (1:10,000) in vitro on Trypanosoma 

 equiperdum and Leishmania donovani. Not active 

 on Endamoeba histolytica or fungi (2). Proactino- 

 mycins A, B, and C have the same qualitative 

 activity, V:)ut B is onh^ one half as active as A and 

 C. A has only slight activity in mice against 

 Streptococcus pneumoniae infections (4). 



Toxicity: LD50 (mice) A: 150 mg per kg, B: 120 

 mg per kg, C: 80 mg per kg intravenously. Com- 

 plex: 90 mg per kg. Mice tolerate 100 mg per kg 

 orally of A, B, and C, and 100 mg per kg sub- 

 cut aneously of A (2). About 100 mg i)er kg of the 

 complex is tolerated intraperitoneally (1). A 

 dilution of 1:3000 kills leucocytes in 1 hovu-; 

 1:10,000 is relatively nontoxic (1). 



References: 



1. Gardner, A. D. and Chain, E. Brit. J. 



Exptl. Pathol. 23: 123-127, 1942. 



2. Florey, H. W. et al. Brit. J. Exptl. Pathol. 



26: 337-349, 1945. 



3. Marston. R. Q. Brit. J. Exptl. Pathol. :{(•: 



398-407, 1949. 



4. Marston, R. Q. and Florey, H. W. Brit. J. 



Exptl. Pathol. 30: 407-418, 1949. 



5. DeSomer, P. (liorn. microbiol. 2: 216-232 



1956. 



Prodigiosin-like Antibiotic 



Produced by: Streptomyces spp. resemliliiig S. 

 ruber. 



Method of extraction: Mycelium extracted with 

 lienzene in the presence of excess ammonium 

 hydroxide. Concentrated extract gives a precipi- 

 tate following treatment with gaseous HCl. Puri- 

 fication by chromatography on acid-washed alumi- 

 niuii oxide. Further purification by countercurrent 

 distribvition (])etroleum ether-benzene-ethanol- 

 0.1 A' HCl, 4:1:3:2). Crystallized from petroleum 

 ether (1). 



Chemical and physical properties: Base: Orange 

 crystals. Partial melting at 147-149°C, followed by 

 recrystallization of the melted portion as the 

 temperature rises; m.p. 203-204°C. Soluble in some 

 organic solvents (1). Xmax 294, 331, 471, 529 (90 per 

 cent in ethanol or 90 per cent in ethanol with 0.1 

 N NaOH). Infrared spectrum given in reference 

 1. Contains two pyrrole rings, one of which has a 

 /i-niethoxyl group (2). C25H35ON3 : C = 76.78%; 

 H = 8.81%; N = 10.33% (1). Hydrochloride: 

 Violet tabular crystals; m.p. 205-209°C. Soluble in 

 most organic solvents, Init not in petroleum ether. 

 Insoluble in water. X„k,x about 295, 357 (broad low 

 peak), 397, and 538 (95 per cent in ethanol) (1,2). 



Biological activity: Moderately active on gram- 



