DESCRIPTIONS OF ANTIBIOTICS 



391 



Toxicity: LDoo (mice) 145 to 170 mg per kg in- 

 travenously, 330 to 355 mg per kg intraperitone- 

 ally, 400 mg per kg subcutaneously, 4250 mg per 

 kg orally (7, 16, 25). LD50 (rats) 128 to 220 mg per 

 kg intravenously, 320 mg per kg intraperitoneally, 

 >3000 mg per kg orally (7, 16). LD50 (lO-day-old 

 chick embryos) 3.2 mg, via allantoic cavity (37). 

 Minimal concentration causing mitosis inhibition 

 in HeLa cells is 125 Mg per ml (30). Highest con- 

 centration permitting epithelial cell migration in 

 tissue culture is 140 ng per ml (42). Inhibits chloro- 

 phyll formation only at levels toxic to plant 

 growth (17). 



Utilization: Application clinically is essentially 

 like that of chlortetracycline or oxvtetracycline. 



References : 



1. Stephens, C. R. et al. 



74:4976-4977, 1952. 



2. Boothe, J. H. ct al . 



75: 4621, 1953. 



3. Conover, L. H. et al. 



75: 4622-4623, 1953. 



4. Boothe, J. H. et al. 



1953-1954, pp. 46-48. 



5. Bohonos, N. et al. Antibiotics Ann. 



1954, pp. 49-55. 



6. Kiser, J. S. et al. Antibiotics Ann. 



1954, pp. 56-62. 



7. Cunningham, R. W. et al. 



1953-1954, pp. 63-69. 



8. English, A. R. et al. 



1953-1954, pp. 70-80. 



9. Minieri, P. P. et al. 



1953-1954, pp. 81-87. 



10. Horvath, D. T. and VanderNoot, 0. W. 



J. Animal Sci. 13: 899-903, 1954. 



11. Palencia, L. et al. Rev. inst. salubridad y 



enfermidad. trop. (Mex.) 14: 113-116, 

 1954. 



12. English, A. R. et al. Antibiotics & Chem- 



otherapy 4: 1082-1085, 1954. 



13. Waddington, W. S. et al. Am. J. Med. Sci. 



228: 164-173, 1954. 



14. Dukes, CD. and Tettenbaum, I. S. Anti- 



biotics Ann. 1954-1955, pp. 674-677. 



15. Eaton, M. Antibiotics Ann. 1954-1955, 



pp. 1046-1049. 



16. Maffii, G. and Mainardi, L. 11 Farm. 10: 



197-210, 1955. 



17. von Euler, H. and Stein, M. L. Experi- 



entia 11: 108-110, 1955. 



18. Meyer, K. F. and Eddie, B. Antibiotics & 



Chemotherapy 5: 289-299, 1955. 



19. Gourevitch, A. et al. Antibiotics & Chem- 



otherapy 5: 448-452, 1955. 



J. Am. Chem. Soc. 

 J. Am. Chem. Soc. 

 J. Am. Chem. Soc. 

 Antibiotics Ann. 

 1953- 

 1953- 

 Antibiotics Ann. 

 Anlii)iotics Ann. 

 Antibiotics Ann. 



20. Conover, L. H. U. S. Patent 2,699,054, 



January 11, 1955. 



21. Gourevitch, A. and Lein, J. U. S. Patent 



2,712,517, July 5, 1955. 



22. Moreng, R. E. et al. N. Dakota Agr. Expt. 



Sta. Bull. 398, June 1955. 



23. Katz, E. J. Infectious Diseases 98: 177- 



186, 1956. 



24. Ogawa, H. and Ito, T. J. Agr. Chem. Soc. 



Japan 30: 123-125, 1956. 



25. Minieri, P. P. et al. U. S. Patent 2,734,018, 



Februarj' 7, 1956. 



26. Lein, J. and Gourevitch, A. U. S. Patent 



2,739,924, March 27, 1956. 



27. Ark, P. A. and Silbray, W. S. Plant Dis- 



ease Reptr. 41 : 449-451 , 1957. 



28. Williams, L. E. Plant Disease Reptr. 41: 



919-922, 1957. 



29. Loo, T. L. et al. Science 126: 253-254, 



1957. 



30. Nitta, K. Japan. J. Med. Sci. & Biol. 10: 



277-286, 1957. 



31. British Patent 770,065, March 13, 1957. 



32. British Patent 775,115, May 22, 1957. 



33. British Patent 775,139, May 22, 1957. 



34. British Patent 775,916, May 29, 1957. 



35. British Patent 779,290, July 17, 1957. 



36. British Patent 787,895, December 18, 1957. 



37. Gentry, R. F. Avian Diseases 2: 76-82, 



1958. 



38. British Patent 790,953, February 19, 1958. 



39. British Patent 799,051, July 30, 1958. 



40. Vandeputte, J. and Heuser, L. J. U. S. 



Patent 2,847,471, August 12, 1958. 



41. DiCarlo,V. Acta Med. Ital. Mai. e Parasit. 



13: 141-144, 1958. 



42. Lawrence, J. C. Brit. J. Pharmacol. 14: 



168-173, 1959. 



Tetrac> cliiies Derivatives 



Produced by: Chemical transformation; Strepto- 

 mycci aiireofaciens (9). 



Chemical and physical properties: I. Ejjimers of 

 tetracycline and anhydrotetracycline are de- 

 scribed in references 3,4, and 7. Separation of the 

 various tetracyclines and their epimers (quatri- 

 mycins) by paper chromatography (5, 6) and by 

 countercurrent distribution (8) has been reported. 

 II. Tetracycline-related compounds which have 

 no biological activity are produced l)y S. aureo- 

 faciens (9). III. Derivatives, including anhy- 

 drochlortetracycline and 9-t-butylanhydrochlor- 

 tetracycline among others, are described in 

 reference 2. 



Biological activity: Anhj-drotetracj'clines, as 



