DESCRIPTIONS OF ANTIBIOTICS 



363 



aftivity than the Na salt (4, 8). In vivo: Active on 

 Yoshida sarcoma (in ova and rats), Ehrlich car- 

 cinoma (ascitic and solid forms) in mice, increas- 

 ing survival time and lowering transplantability 

 of tumors (2, 13). Active on sarcoma 180 (ascitic 

 form, mice), Usubuchi sarcoma (rats) (13), 

 Takeda sarcoma (rats), ascites hepatoma 7974 

 (rats) (16), carcinoma 1025, Krebs 2 ascites car- 

 cinoma, Harding-Passey melanoma (moderate 

 activity) (26), RC mammary adenocarcinoma 

 (mice) (37) and Crabb hamster sarcoma (34). 

 Histologically, incidence of mitosis is decreased 

 (11). Destroys tumor cells at both resting and 

 tlividing stages (15). Causes desquamation and 

 loss of transferability in HeLa cells, an effect not 

 reversed by cysteine (13). Synthetic d- and 1-forms 

 of sarkomycin have the same antitumor activity 

 as the dl-form against Ehrlich ascites carcinoma 

 (mice), Init lower antil)acterial activity (27, 30). 

 Sarkoini/cin B: Weak or no antibacterial activity; 

 some antitumor activity (33). Sarkomycin E: 

 active on cancer cells, Staph, aureus, and Micro- 

 coccus flavus (35). "M crystal": Biologically inac- 

 tive. Sarkomycin Si .• Has 10 per cent of the activ- 

 ity of sarkomycin on Staph, aureus, equal activity 

 on Micrococcus flavus, greater activity on ('. albi- 

 cans, no antitrichomonal activity, 25 per cent of 

 the anti-HeLa cell activity, and 50 per cent of 

 the antitumor activity (21, 25). Sarkomycin S-2 : 

 Has 60 per cent of the anti-.l//r;-ococcHS activity of 

 .sarkomycin, and slight antitumor activity (21). 



Scheme 3. Sarkomycin rearrangement i)roduct: 

 2-methyl-3-o.\o-l-cyclopentanecarbo.\ylic acid. 



H,C — 



H 

 -C— COOH 



H 

 HOOC— C ■ 



-CHj— 



-CHj 



H.C 

 H.2C 



■0-- ^c 



ScHE.ME 4. Sarkomycin B 



H H 



-C— COOH HOOC— C- 



C CH., CH2 CH 



CHo 



I 

 CH.> 



OH 



Scheme 5. Sarkomvcin E 



H.2C- 

 H.C 



H 

 C— COOH HOOC— C- 



C CH. 



-CH2 CH 



CH.. 



I 

 CH2 



Sche.me 6. ;M-crvstal 



H.C- 



H 

 -C— COOH 



H 



HOOC— C- 



CH2 



H..C CH— CH.>— S— S— CHo— CH CH-. 



\c/ ' \c/ 



o 



o 



Scheme 7. Sarkomvcin Si 



Scheme 9. Analogue a: 5-methylenecyclopenta- 

 none-3-carl)o.\vlic acid. 



H2C=C- 

 0=C 



H.. 



-CH2 



C— COOCH3 

 H 



Scheme 10. Analogue b: methyl-5-methylenecy- 

 clopentanone-3-carbo.\ylate. 



Sarkomycin S3 : Has 220 per cent of the antimi- 

 crococcal activity of sarkomj^cin, increa.sed anti- 

 Candida activity, moderate antitvmior activity, 

 but no antitrichomonal activity (21, 22, 36). 

 Dihydrosarkomycin: No antibacterial or anti- 

 HeLa cell activity. Active on Ehrlich ascites car- 

 cinoma (25). 



Toxicity: Sarkomycin: LDs,, (mice) 800 to 1600 

 mg per kg intravenously, 400 to 800 mg per kg 

 subcutaneously, and 1 to 1.8 gm per kg intraperi- 

 toneally (4, 11). Mice tolerate 4.8 gm per kg orally 

 (8). Addition of glutathione, cysteine, or serum 

 reduces toxicity (4). Na salt causes necrosis at 

 site of subcutaneous administration; Ca salt 



