DEi^CRIPTIOXS OF ANTIBIOTICS 



367 



greater than that expected from in vitro tests, and 

 may be accounted for by the verj' high concentra- 

 tions attained in the tissues (25). 



Toxicity: Complex: LD50 (mice) 1.25 to 2.5 gm 

 per kg subcutaneously (6, 9, 12, 19), 168 mg per 

 kg intravenously, and 5 gm per kg orally (6, 9). 

 LDoo (rats) 9.4 ± 0.8 gm per kg orally. LD50 (dogs) 

 5.2 ± 1.6 gm per kg orally (21). Spiramycins I, II, 

 and III do not differ in toxicity (6, 9). Gastrointes- 

 tinal disturbances occur in some patients (21). 



Utilization: Staphylococcal infections resistant 

 to other drugs. Pneumococcal infections, whoop- 

 ing cough, urethritis (15, 23), ocular and other 

 infections (23, 24). Low serum concentrations re- 

 ported following administration (7). Active on 

 coccidiosis (Eimeria tenella) in chickens. Malarial 

 infections (14). Possible use in amoebic dysentery 

 (10). 



Spiramycin Derivatives 



Produced by: Hj'drogenation of spiramycins 

 (19). Derivatives of spiramycins. 



Method of production of neospiratnycins: Spira- 

 mycins are kept at 20-50°C in water, ethanol, or 

 an ethanol-water mixture at pH 3 to 5 until the 

 biological activity against B. subtilis becomes 

 constant. Neospiramycins I, II, and III are thus 

 formed from spiramycins I, II, and III, respec- 

 tively. Separated by extracting with a mixture of 

 isopropyl ether-isopropanol-buffer (pH 8) or ben- 

 zene-buffer (pH 5 to 8) mixture, or by chromatog- 

 raphy on alumina (26). 



Chemical and physical properties: H ydrogenation 

 products: Dihydrospiramycin I: m.p. 128-132°C. 

 [a Id = —83° (c = 1 per cent in methanol). Tetra- 

 hydrospiramycin I: m.p. 132-135°C. [a.]^^ = —79° 

 (c = 1 per cent in methanol). Tetrahydrospira- 

 mycin II: m.p. 125-128°C. [aj^ = —63° (c = 1 per 

 cent in methanol). Tetrahydrospiramycin III: 

 m.p. 135-140°C. [a]" = -71° (c = 1 per cent in 

 methanol). All the tetrahydro derivatives have a 

 light -absorption spectrum maximum at 820 niju. 

 More highlj^ hj^drogenated products are inactive 

 biologically (19). 



Biological activity: Tetrahydro derivatives have 

 less activity than the parent compounds on Staph, 

 aureus, K. pneumoniae, D. pneumoniae, and 

 Corynebacterium pseudodiphtheriticum, but more 

 on B. cereus, Micrococcus citreus, Sarcma lutea, 

 and Streptococcus viridans. Equally active as the 

 parent compounds on Streptococcus and D. pneu- 

 moniae infections in mice (19). Neospiramycins: 

 More active than spiramycins on certain organ- 

 isms (26). 



Toxicity: Hydrogenation derivatives: LDsu (mice) 



1.35 gm per kg subcutaneously (19). Neospira- 

 mycins: Less toxic than spiramycins (26). 

 References: 



1. Pinnert-Sindico, S. Ann. inst. Pasteur 6: 



702-707, 1954. 



2. Giroud, P. Bull. soc. pathol. exotique 47: 



642-644, 1954. 



3. Boqacz, J. Bull. soc. pathol. exoticjue 47: 



903-913, 1954. 



4. Pinnert-Sindico, S. et al. Antibiotics Ann. 



724-727, 1954-1955. 



5. Boqacz, J. et al. Pres.se med. 91, 1955. 



6. DiMarco, A. and Ghione, M. Atti soc. lom- 



barda sci. med. e biol. 10: 102-106, 1955. 



7. Lepper, M. H. et al. Antibiotics Ann. 



658-666, 1955-1956. 



8. Pinnert-Sindico, S. and Pellerat, J. Thera- 



pie 11: 308-323, 1956. 



9. Cosar, C. Therapie 11:324-328,1956. 



10. Charmot, G. and Delahousse, Y. Bull. soc. 



pathol. exotique 49: 365-373, 1956. 



11. Barme, M. Bull. soc. pathol. exotique 49: 



1085-1089, 1956. 



12. British Patent 758,726, October 10, 1956. 



13. Corbaz, R. et al. Helv. Chim. Acta 39: 



304-317, 1956. 



14. Cuckler, A. C. and Malanga, C. M. Anti- 



biotics Ann. 1956-1957, pp. 592-595. 



15. Durel, P. Giorn. ital. chemioterap. 4: 



243-250, 1957. 



16. Paul, R. and Tchelitcheff, S. Bull. soc. 



chim. France 443-447, 1957. 



17. Paul, R. and Tchelitcheff, S. Bull. soc. 



chim. France 7.34-737, 1957. 



18. Paul, R. and Tchelitcheff, S. Bull. soc. 



chim. France 1059-1064, 1957. 



19. British Patent 785,191, October 23, 1957. 



20. British Patent 785,098, October 23, 1957. 



21. Boyd, E. M. Can. J. Biochem. Physiol. 



36: 103-110, 1958. 



22. Maral, R. and Ciaccio, G. Compt. rend. 



soc. biol. 1.52: 49-52, 1958. 



23. David, N. A. and Porter, G. A. Antibiotics 



Ann. 1958-1959, pp. 188-198. 



24. Hurwitz, P. Antiliiotics Ann. 1958-1959, 



pp. 199-201. 



25. Benazet, F. antl Dubost, ^I. Antibiotics 



Ann. 1958-1959, pp. 211-220. 



26. British Patent 801,536, September 17, 1958. 



27. Gaumann, E. and Prelog, V. Swiss Patent 



334-468, January 15, 1959. 



Stapliylomycin 



Produced by: Streptomyces virginiae (3). 

 Synonyms: Antibiotic 899. Factor Mi of staphjd- 



