FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. III. Antitumor activities on experimental tumors in mice.
FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. III. Antitumor activities on experimental tumors in mice.
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DOI：
10.7164/antibiotics.47.315
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发表时间：
1994-03
期刊：
影响因子：
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通讯作者：
H. Ueda;T. Manda;S. Matsumoto;S. Mukumoto;F. Nishigaki;I. Kawamura;K. Shimomura
中科院分区：
文献类型：
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作者：
H. Ueda;T. Manda;S. Matsumoto;S. Mukumoto;F. Nishigaki;I. Kawamura;K. Shimomura
研究了从紫色色杆菌968中分离的（E）-（1 S，4S，10 S，21 R）-7-[（Z）-亚乙基]-4，21-二异丙基-2-氧杂-12，13-二硫杂-5，8，20，23-四氮杂双环[8，7，6]-二十三碳-16-烯-3，6，9，19，22-戊酮的抗肿瘤活性。FR 901228（ip）延长了携带诸如P388和L1210白血病以及B16黑色素瘤的小鼠腹水肿瘤的小鼠的寿命，并且抑制（iv）小鼠实体瘤的生长（结肠38癌、M5076网状细胞肉瘤和甲硫氨酸纤维肉瘤）和人实体瘤（Lu-65和LC-6肺癌，和SC-6胃腺癌）分别植入正常和裸鼠。其抗肿瘤活性对丝裂霉素C或顺铂难治的小鼠Meth A纤维肉瘤和人SC-6胃腺癌特别有效。FR 901228在小鼠中对丝裂霉素C、环磷酰胺、长春新碱和5-氟尿嘧啶耐药的P388白血病也比对非耐药的P388更有效。这些结果表明，FR 901228将成为一种新型的治疗癌症的药物。
The antitumor activities of FR901228, (E)-(1S,4S,10S,21R)-7-[(Z)- ethylidene]-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23- tetraazabicyclo[8,7,6]-tricos-16-ene-3,6,9,19,22-pentanone, isolated from Chromobacterium violaceum No. 968, were studied in animals. FR901228 (ip) prolonged the life of mice bearing such murine ascitic tumors as P388 and L1210 leukemias and B16 melanoma, and inhibited (iv) the growth of murine solid tumors (Colon 38 carcinoma, M5076 reticulum cell sarcoma and Meth A fibrosarcoma) and human solid tumors (Lu-65 and LC-6 lung carcinomas, and SC-6 stomach adenocarcinoma) implanted in normal and nude mice, respectively. Its antitumor activity was especially potent against murine Meth A fibrosarcoma and human SC-6 stomach adenocarcinoma which were refractory to mitomycin C or cisplatin. FR901228 also was more effective against mitomycin C-, cyclophosphamide-, vincristine- and 5-fluorouracil-resistant P388 leukemias than against non-resistant P388 in mice. These results suggest that FR901228 will be a new type of drug for the treatment of cancer.