从栖空气生糖丝菌ATCC 39243中生产、分离及鉴定新型氟代吲哚咔唑

Production, isolation and structure determination of novel fluoroindolocarbazoles from Saccharothrix aerocolonigenes ATCC 39243.

作者信息

Lam K S, Schroeder D R, Veitch J M, Colson K L, Matson J A, Rose W C, Doyle T W, Forenza S

机构信息

Bristol-Meyers Squibb Company, Pharmaceutical Research Institute, Wallingford, CT 06492, USA.

出版信息

J Antibiot (Tokyo). 2001 Jan;54(1):1-9. doi: 10.7164/antibiotics.54.1.

DOI:10.7164/antibiotics.54.1

PMID:11269705

Abstract

Saccharothrix aerocolonigenes ATCC 39243 produces an indolocarbazole antitumor agent rebeccamycin under submerged fermentation conditions. Adding DL-6-fluorotryptophan to culture of S. aerocolonigenes ATCC 39243 induces the formation of two novel indolocarbazoles, fluoroindolocarbazoles A and B. Feeding DL-5-fluorotryptophan to culture of S. aerocolonigenes ATCC 39243 induces the production of a novel indolocarbazole, fluoroindolocarbazole C. These fluoroindolocarbazoles have been isolated from culture broth and purified to homogeneity by vacuum liquid chromatography and column chromatography. All three fluoroindolocarbazoles are more potent than rebeccamycin against P388 leukemia by ip route in murine model.

摘要

栖棉糖丝菌ATCC 39243在深层发酵条件下产生吲哚咔唑类抗肿瘤剂瑞贝卡霉素。向栖棉糖丝菌ATCC 39243的培养物中添加DL-6-氟色氨酸可诱导形成两种新型吲哚咔唑类化合物，即氟吲哚咔唑A和B。向栖棉糖丝菌ATCC 39243的培养物中添加DL-5-氟色氨酸可诱导产生一种新型吲哚咔唑类化合物，即氟吲哚咔唑C。这些氟吲哚咔唑类化合物已从培养液中分离出来，并通过真空液相色谱法和柱色谱法纯化至同质。在小鼠模型中，通过腹腔注射途径，所有三种氟吲哚咔唑类化合物对P388白血病的活性均比瑞贝卡霉素更强。