新型哺乳动物细胞周期抑制剂——烟曲霉产生的色氨酸蛋白酶抑制剂A、B及其他二酮哌嗪。I. 分类学、发酵、分离及生物学特性

Novel mammalian cell cycle inhibitors, tryprostatins A, B and other diketopiperazines produced by Aspergillus fumigatus. I. Taxonomy, fermentation, isolation and biological properties.

作者信息

Cui C B, Kakeya H, Okada G, Onose R, Osada H

机构信息

Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.

出版信息

J Antibiot (Tokyo). 1996 Jun;49(6):527-33. doi: 10.7164/antibiotics.49.527.

DOI:10.7164/antibiotics.49.527

PMID:8698634

Abstract

Two novel diketopiperazines named tryprostatins A (1) and B (2) and a new natural product belonging to the diketopiperazine series, designated as demethoxyfumitremorgin C (3), together with four known diketopiperazines, fumitremorgin C (4), 12,13-dihydroxyfumitremorgin C (5), fumitremorgin B (6) and verruculogen (7), were isolated from the fermentation broth of Aspergillus fumigatus BM939 by the combined use of solvent extraction, silica gel column chromatography, preparative TLC and repeated-preparative HPLC. The diketopiperazines showed an inhibitory activity on the cell cycle progression of mouse tsFT210 cells in the M phase with the MIC values of 16.4 microM (1), 4.4 microM (2), 0.45 microM (3), 4.1 microM (4), 60.8 microM (5), 26.1 microM (6) and 12.2 microM (7), respectively.

摘要

通过溶剂萃取、硅胶柱色谱、制备薄层层析和反复制备高效液相色谱联用的方法，从烟曲霉BM939的发酵液中分离出两种新型二酮哌嗪，分别命名为曲前列他汀A（1）和B（2），以及一种属于二酮哌嗪系列的新天然产物，命名为去甲氧基烟曲霉震颤素C（3），同时还分离出四种已知的二酮哌嗪，烟曲霉震颤素C（4）、12,13 - 二羟基烟曲霉震颤素C（5）、烟曲霉震颤素B（6）和疣孢菌素（7）。这些二酮哌嗪对处于M期的小鼠tsFT210细胞的细胞周期进程具有抑制活性，其最小抑菌浓度（MIC）值分别为16.4微摩尔/升（1）、4.4微摩尔/升（2）、0.45微摩尔/升（3）、4.1微摩尔/升（4）、60.8微摩尔/升（5）、26.1微摩尔/升（6）和12.2微摩尔/升（7）。