UCH9，一种由链霉菌产生的新型抗肿瘤抗生素：I. 产生菌、发酵、分离及生物活性

UCH9, a new antitumor antibiotic produced by Streptomyces: I. Producing organism, fermentation, isolation and biological activities.

作者信息

Ogawa H, Yamashita Y, Katahira R, Chiba S, Iwasaki T, Ashizawa T, Nakano H

机构信息

Tokyo Research Laboratories, Kyowa Hakko Kogyo, Japan.

出版信息

J Antibiot (Tokyo). 1998 Mar;51(3):261-6. doi: 10.7164/antibiotics.51.261.

DOI:10.7164/antibiotics.51.261

PMID:9589060

Abstract

We developed a microbial prescreen using Bacillus stearothermophilus NUB3620 and bacteriophage TP-68 to detect potential antitumor compounds acting on DNA or topoisomerases. During the course of screening microbial cultures for their antibacteriophage activities, we found that Streptomyces sp. isolated from a soil sample collected in Iwakuni city, Yamaguchi prefecture, Japan, produced a new antitumor antibiotic, UCH9. UCH9 was isolated from culture broth by a combination of EtOAc extraction and column chromatography. UCH9 has a new structure related to the antitumor antibiotic chromomycins. It exhibited antimicrobial activity against Gram-positive organisms. UCH9 also showed cytotoxic activity against HeLa S3 cells with an IC50 value of 13 nM and exhibited antitumor activity in vivo against mouse leukemia P388.

摘要

我们开发了一种微生物预筛选方法，使用嗜热脂肪芽孢杆菌NUB3620和噬菌体TP-68来检测作用于DNA或拓扑异构酶的潜在抗肿瘤化合物。在筛选微生物培养物的抗噬菌体活性过程中，我们发现从日本山口县岩国市采集的土壤样本中分离出的链霉菌属产生了一种新的抗肿瘤抗生素UCH9。UCH9通过乙酸乙酯萃取和柱色谱相结合的方法从培养液中分离得到。UCH9具有与抗肿瘤抗生素色霉素相关的新结构。它对革兰氏阳性菌具有抗菌活性。UCH9对HeLa S3细胞也表现出细胞毒性活性，IC50值为13 nM，并在体内对小鼠白血病P388表现出抗肿瘤活性。