288 



DESCRII'TIOXS OF ANTIBIOTICS 



genated; j-ield^ a biologicall)- inactive tetraacetate 

 (7). Stable to boiling for 10 minutes at pH 3.7; less 

 stable at pH 9.0 and above (I) . 2 ,4-Dinitrophenijl- 

 hydrazone derivative: Yellow crystalline substance; 

 m.p. 154-156°C (6, 7). Acid hydrolysis products of 

 hygromycin include neo-inosamine-2 (5, (i). Alka- 

 line hydrolysis yields 3,4-dihydroxy-a-methylcin- 

 namic acid. The sugar in hygromycin is 5-keto-6- 

 desoxyarabohexose, C-i.iHigNOri : C = 53.85%; 

 H = 6.15%; N = 2.78%; O = 37.53%; C— Me = 

 2.56%. The possible structure of hygromycin (6) 

 is discussed in Chapter 6. 



Biological activity: Active on certain gram- 

 positive and gram-negative bacteria, mycobac- 

 teria, and actinomycetes at 3 to 51 jug per ml (1). 

 Active on Endamoeba histolytica and Leptcjspira 

 pomona (11). Very active on pleuropneumonia- 

 like organisms (9). Activity on K. pneumoniae 

 inhibited by cysteine. Activity unaffected by pH. 

 Rate at which resistance develops depends on the 

 microorganism used. Active in mice on M. tubercu- 

 losis H37I{v, l)Ut only one third to one fifth the 

 activity of streptomycin. Also active in mice on 

 Streptococcus pyogenes and Borrelia novyi, and 

 moderately active on K. pneumoniae. Also active 

 against mouse meningopneumonitis infections. 

 Not active against viruses such as "MM" and 

 Semiliki Forest viruses (1, 7). Active on E. his- 

 tolytica (rats) and oxyurids (mice) (11). 



Toxicity: Mice tolerate 2 gm per kg intrave- 

 nously and subcutaneously (7). 



I'tilization: Prevention of bacterial decomposi- 

 tion of fish stickwater (4). Used in animal feeds 

 for prevention and cure of large round worms, 

 nodular worms, and whipworms (10). 



References : 



1. Pittenger, R. C. ct al. Antil)iotics & 



Chemotherapy 3: 121)8-1278, 1953. 



2. Mann, R. L. et al. Antibiotics & Chemo- 



therapy 3: 1279-1282, 1953. 



3. Sumiki, Y. et al. J. Antibiotics (Japan) 



8A: 170, 1955. 



4. Idler, D. R. et al. Appl. Microbiol. 3: 



265-268, 1955. 



5. Isono, K. et al. J. Antibiotics (Japan) 



9A: 225, 1956. 



6. Mann, R. L. and Woolf, 1). O. J. Am. 



Chem. Soc. 79: 120-126, 1957. 



7. Isono, K. et al. J. Antibiotics (Japan) 



lOA: 21-30, 1957. 



8. Namiki, M. et al . J. .\n1 il)iotics (Japan) 



lOA: 160-170, 1957. 



9. Wick, W. E. and Holmes, 1). H. Bacteriol. 



Proc. 21-22, 1958. 



10. Conrad, J. H. and Beeson, W. M. Purdue 



Univ. Agr. Expt. Sta. Mimeo. AH 233, 

 May, 1958. 



11. McCowen, M. C. et al. Antibiotics Ann. 



883-886, 1956-1957. 



12. Handy, A. H. et al. Poultry Sci. 36: 748- 



754, 1957. 



Hygromycin B 



Produced by: Streptcmyces hygroscopicus. 



Method of extraction: Broth treated with Amber- 

 lite IRC-50 (Na+ cycle). Elution with 0.1 .V HCl. 

 Eluate treated with carbon at pH 10.5. Hygro- 

 mycin B eluted with a mixture of concentrated 

 NH4()H, water, and acetone (1:3:6). Eluate con- 

 centrated and antibiotic precipitated with ace- 

 tone. Precipitate dissolved in methanol. Repre- 

 cipitation with ether. Further purification by 

 adsorption on Amberlite IRC-50 (Li+ cycle) and 

 elution with 29 per cent NH4OH (1). 



Chemical and physical properties: Polyhydroxy 

 l)ase. Amorphous powder. Melts over wide range 

 about 180°C. C1.5H28N2O9-10. Very soluble in 

 water and methanol; essentially insoluble in less 

 polar solvents. Two titrable basic groups: pKa' 

 7.1 and pKa' 8.8. No absorption ot ultraviolet 

 light. Infrared data given in reference 1. Positive 

 anthrone and Molisch tests. Negative Benedict 

 and Fehling tests. Forms a crystalline p-(p'- 

 hydroxyphenylazo)benzenesulfonic acid salt. 



Biological activity: Moderate activity on gram- 

 positive and gram-negative bacteria and fungi 

 (6.2 to 100 Mg per ml). Very active on helminths, 

 including ascarids, in swine (1). Increases growth 

 rate of baby pigs when added to the diet (2). 



Utilization : .\nthelmintic. 



References: 



1. Mann, R. L. and Bromer, W. W. J. Am. 



Chem. Soc. 80: 2714-2716, 1958. 



2. Teague. H. S. and Rut ledge, E. A. Ohio 



Agr. Expt. Sta. Mimeo 114, July, 1959. 



H> fir*>niycin-like Aiitihiolic 



Produced by: Streptomyces sp. 



Synonyms: Antibiotic 1703-18B. Similar, Imt 

 not identical, to hygromycin (1). 



Chemical and physical properties: Acid hy- 

 drolysis products include: neo-inosamine-2 (1) 

 and the 3,4-dihydroxy-a-methylcinnamic acid 

 amide of neo-inosamine-2. The latter is isomeric, 

 and possibly identical with, the corresponding 

 degradation i)roduct of hygromycin (2). Structure 

 of the degradation product: 



