DESCRIPTIONS OF ANTIBIOTICS 



163 



bacteria and M. phlei. Not active on other myco- 

 bacteria, gram-negative bacteria, or C. albicans. 

 Is 64 times more active on Staph, aureus at pH 6.0 

 than at pH 8.5. Some antitmiior activity in mice 

 against the ascitic form of Ehrlich carcinoma and 

 the solid form of Crocker sarcoma 180. 



Toxicity: LD50 (mice) 2 mgper kg intravenously, 

 and 2.5 mg per kg subcutaneously. Not well 

 absorbed from intestinal tract. 



Reference: 1. Nishimura, H. et al. J. Antilnotics 

 (Japan) 1(»A: 205-212, 1957. 



Abiiraniycin Isomer 



Produced by: Streptomyces sjj. differing from 

 S. aburaviensis . 



Synonym: Antibiotic M5-18903. Both aburamy- 

 cin and its isomer have similarities with aureolic 

 acid. 



Method oj extraction : I. Broth-filtrate extracted 

 with chloroform at pH 7.2 to 7.5. Precipitated from 

 extract by addition of petroleum ether. Chromato- 

 graphed on alumina with chloroform as solvent 

 and developer. Elated with 5 per cent ethanol in 

 chloroform. Active fractions concentrated under 

 reduced pressure and precipitated with petroleum 

 ether. Crystallized from chloroform on addition 

 of petroleum ether. II. Same as that for aburamy- 

 cin. 



Chemical and physical properties: Weakly acidic 

 substance. Yellow crystals; m.p. 169-171°C. 

 Soluble in chloroform, acetone, pyridine, ethyl 

 acetate, dimethylformamide, ethanol, and meth- 

 anol. Insoluble in water and petroleum ether. 

 Ultraviolet absorption spectrum maxima at 227 

 n\^l (E/e'm 200 ± 5), 278 m^ (£'i'cm 400 ± 10), and 400 

 mix. Weak maxima at 304, 317 (E'l'L 60 ± 2), and 

 330 viXix (ethanol). Infrared spectrum given in 

 reference 1. [aj" = —29° (c = 0.5 per cent in 

 methanol). pKl = 7.1. C = 53.32%; H = 7.44%; 

 = 35.24%. No N, S, or halogen. Molecular 

 weight, 1295. Paper chromatographic l)ehavior is 

 indistinguishable from aburamycin. Can be hydro- 

 genated to yield a biologically active compound 

 which has similar ultraviolet spectra in alkaline 

 and acid solution to the hydrogenated product 

 from aureolic acid. Acetylation of the hydro- 

 genated product destroys the biological activity. 

 The acetyl derivative has m.p. at 205-207°C. 



Biological activity: Active on gram-i)ositive 

 bacteria, including mycobacteria. Not active on 

 gram-negative bacteria. Not active on bacteria 

 in vivo. Some activity on Endamoeba histolytica in 

 vivo. Reduces the worm burden in mice infected 

 with Syphacia obvelata. Some protection against 



leukemia P-1534 in mice, but no activity on sar- 

 coma 180. 



Toxicity: LD50 (mice) 2 mg per kg intravenously. 

 Mice tolerate a single oral dose of 80 mg per kg. 

 The antibiotic was shown to be unabsorbed from 

 the injection site. 



Reference: 1. Gale, R. M. et al. Antibiotics Ann. 

 489-492, 1958-1959. 



Acetoniycin 



Produced by: Streptomyces ramiilosis (1). 



Method of extraction: Broth filtered with a filter- 

 aid, and filtrate extracted with ethyl acetate. 

 Extract concentrated in vacuo. Addition of petro- 

 leum ether to the residue precipitated acetomycin. 

 Crystallized in the cold from hot methanol (1). 



Chemical and physical properties: Neutral, 

 saturated, ketoacetoxy lactone, with three 

 methyl groups. Colorless, rough rod-like crystals. 

 Sublimes at 70°C; m.p. 115-116°C. [a|„ = -167° 

 (c = 1.47 per cent in ethanol). CuiHuOs: 

 C = 55.96%; H = 6.65%; O = 37.31%. No ultra- 

 violet absorption. Infrared spectrum given in 

 reference 1. Forms a mono-2,4-nitrophenylhy- 

 drazone: dark yellow crystalline leaves; m.p. 205- 

 208°C. Positive iodoform reaction. Negative FeCls 

 test. Structural formula given in Chapter 6. 



Bi-jlogical activity: Weak activity on gram- 

 positive and gram-negative bacteria (100 ^g per 

 ml); moderateh' active on M. tuberculosis H37Rv 

 (10 fig per ml), Trichomonas foetus (25 /ig per ml), 

 and E. histolytica (70 /ug per ml) (1). 



Toxicity: LD50 (mice) 100 mg per kg subcutane- 

 ously (1). 



References: 



1. Ettlinger, L. et al. Helv. Chim. Acta 41: 



216-219, 1958. 



2. Keller-Schierlein, W. ei al. Helv. Chim. 



Acta 41: 220-228, 1958. 



Achroinoviromycin 



Produced by: Streptomyces achromogenes. 



Remarks: The same strain produces sarcidin. 



Method of extraction: Extraction with ethvl ace- 

 tate at pH 2.0, concentration in vacuo at 40°C. 

 Freeze drying after addition of 2.0 i)er cent 

 NaHCO:, to pH 7.5 



Chemical and physical properties: Negative 

 Molisch, Tollen, ninhydrin, Sakaguchi, Millon, 

 Pauly, and Fed., tests. 



Biological activity: Active in vitro and in vivo 

 against Japanese B encephalitis virus. Not active 

 against western equine encephalitis virus. 



Toxicity: 20 mg per mouse of the crude sul)stance 



