DESCRIPTIONS OF ANTIBIOTICS 



347 



and guinea pigs (14). Curative action on Babesia 

 rodhani infections of mice (30). Active on natural 

 oxyvirid and tapeworm infections in mice (27). 

 Slightly active, in contact tests, on herpes simplex 

 virus infections of mice (23). Some inhibition of 

 the following neoplastic diseases: mammary adeno- 

 carcinoma (C3H mice), 755 mammary adeno- 

 carcinoma (C57BL mice), transplanted leukemia 

 (mice), Lewis bladder carcinoma, Ridgeway osteo- 

 genic sarcoma, Harding-Passey melanoma, 72J 

 mammary carcinoma, 8110 brain carcinoma, car- 

 cinoma 1025, Bashford carcinoma 63, and j\li- 

 yono adenocarcinoma (5, 11, 12, 21, 24, 32). The 

 carcinostatic activity parallels the trypanocidal 

 activity (18), but not the antibacterial activity 

 (24). The antitumor activity of puromycin was 

 shown to reside in the aminonucleoside portion of 

 the molecule (17). (See also "Puromycin Ana- 

 logues" section which follows.) 



Toxicity: LD.io (mice) 335 mg per kg intra- 

 venously, 580 mg per kg intraperitoneally, and 720 

 mg per kg orally. Not irritating to rabbit's eye or 

 l)y parenteral administration (16). 



Utilization: Amoebic dy.sentery (28), chronic 

 amebiasis (13), sleeping sickness (29). Temporary 

 effect on some advanced incurable disseminated 

 neoplastic diseases in human beings (22). 



Purotin/ciu Analogues 



Produced by: Synthesis from j)uromycin (12). 



Chemical and physical properties: Aminonu- 

 i'leoside analogue 2484L: Crystalline substance 

 containing the amino sugar and purine moieties of 

 puromycin; m. p. 215-216°C. [a]f = -24.6° (H-/)). 

 C = 49.4%; H = 6.39%; N = 28.4%. It is 6-di- 

 methylamino-9-(3'-amino-3-desoxy-/3,D-ribopura - 

 iiosyl)purine. Structural formula (12): 



H3C— N— CH, 



N 



-N 



^. 



N' 



..-^ 



NH.. 



CH— CHOH— CH— CH..( )H 



-O- 



Other analogues : These include analogues in which 

 the amino acid moiety has been replaced by a dif- 

 ferent amino acid or a peptide (17). 



Biological activity: Analogue ZJi-SJi-L: Does not 

 have the antibacterial spectrum typical of puro- 

 mycin; 3 to 4 times more active against Trypano- 

 soma equiperdum (17). On a molecular basis, it is 

 equally as active as puromycin against T. equiper- 

 dum (7). It has considerably less activity against 



Endamoeba histolytica infections (guinea pigs) 

 than puromycin (15). This analogue is very active 

 (more so than the parent compound) against 

 transplanted mammary adenocarcinoma in C3H 

 mice and 755 mammary adenocarcinoma in C57BL 

 mice (12, 17, 24). Other analogues: Four amino acid 

 analogues, L-phenylalanyl, glycyl, leucyl, and 

 glycyl-p-methoxy-L-phenylalanyl, have an in- 

 hibitory effect on transplanted mammary adeno- 

 carcinoma of mice and are more active than 

 puromycin. The L-phenylalanyl derivative also 

 has some antileukemic activity (17). Six other 

 analogues, carboethoxyamino, benzylideneamino, 

 a-sodium sulfobenzylamino, L-phenylalanyl- 

 amino, 4-chlorobenzylideneamino, and m-methoxy 

 p-hydroxybenzylideneamino substitutions for 

 the amino acid moiety of puromycin, have activity 

 eciual to the 2484L analogue against Trypanosoma 

 equiperdum (19). Fifteen benzylidene analogues of 

 puromycin were active on mammary adenocarci- 

 nomas in mice (33). 

 References: 



1. Porter, J. N. et al. Antibiotics & Chemo- 



therapy 2: 409-410, 1952. 



2. Hewitt, R. I. et al. Am. J. Trop. Med. Hyg. 



2: 254-266, 1953. 



3. Waller, C. W. (;/ 0/. J. Am. Chem. Soc. 75: 



2025, 1953. 



4. Baker, B. R. and Schaub, R. E. J. Am. 



Chem. Soc. 75: 3864-3865, 1953. 



5. Troy, W. et al. Antibiotics Ann. 186-190, 



1953-1954. 



6. Christen, R. and Thiermann, K. Bol. in- 



form, parasitol. Chile 8: 49-54, 1953. 



7. Hewitt, R. I. et al. Antibiotics (!t Chemo- 



therapy 4: 1222-1227, 1954. 



8. Tobie, E. J. Am. J. Trop. Med. Hyg. 3: 



852-859, 1954. 



9. Baker, B. R. et al. J. Org. Chem. 19: 



631-660, 1954. 



10. Hesseltine, C. W. et al. Mycologia 46: 



16-23, 1954. 



11. Eichorn, P. A. et al. Ann. N. Y. Acad. Sci. 



58: 1172-1182, 1954. 



12. Baker, B. R. et al. J. Am. Chem. Soc. 76: 



2838, 1954. 



13. Faigenbaum, J. and Allja, M. Bol. chileno 



parasitol. 9: 94-99, 1954. 



14. Taylor, D. J. et al. Antibiotics Ann. 745- 



750, 1954-1955. 



15. Bond, H. W. et al. Antil)iotics Ami. 751- 



756. 1954-1955. 



16. Sherman, J. F. et (d. Antil)iotics Ann. 



757-765, 1954-1955. 



17. Bennett, P. L. e/ «/. Antil)iotics Ann. 766- 



769, 1954-1955. 



