- 著者
- KATSUTOSHI TAKAHASHI HISAO EKIMOTO SHOKO AOYAGI AKIKO KOYU HIROSHI KURAMOCHI OSAMU YOSHIOKA AKIRA MATSUDA AKIO FUJII HAMAO UMEZAWA
- 出版者
- JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
- 雑誌
- The Journal of Antibiotics (ISSN:00218820)
- 巻号頁・発行日
- vol.32, no.1, pp.36-42, 1979 (Released:2006-04-12)
- 参考文献数
- 12
- 被引用文献数
- 30 31
Pepleomycin (PEP), 3-[(S)-1'-phenylethylamino]propylaminobleomycin has potent activity and is less pulmonary toxic than bleomycin (BLM). Biological activity and toxicity of the following degradation products of PEP have been studied in detail: the product of carbamoyl migration (ISO), the product of decarbamylation (DC), the product of ring closure of the side chain on the pyrimidine moiety (RC), the depyruvamide product (DP) and the product of an enzymatic inactivation (DA). These degradation products showed much lower activity than PEP in vitro: antimicrobial and anti-HeLa activities, inhibition of DNA synthesis in AH66 cells and the DNA strand cleavage. Acute toxicity and pulmonary toxicity were tested in mice. Results indicated much lower acute toxicity corresponding to the decreased in vitro activity when compared to PEP. DP and RC did not cause lung fibrosis in mice, while ISO and DC showed 1/2.6 and 1/5.7 degree of pulmonary toxicity, respectively, in comparison with PEP.