Development of bioprobes which regulate mammalian cell cycle

癌细胞是一种不受控制的细胞，具有细胞周期的失调，因此，新的细胞周期抑制剂可能是癌症化疗的良好候选者，也可能为阐明细胞周期调节机制提供有用的分子探针。我们已经开始从微生物来源筛选新的细胞周期抑制剂。在筛选过程中，我们通过对小鼠tsFT210细胞周期进程的抑制作用，从真菌曲霉BM939发酵液中分离出新的二酮哌嗪类生物碱，螺型前列腺素A、B、tryprostatins A、B和cyclotryprostatins B、D，以及三种新的天然二酮哌嗪类，cyclotryprostatins A、C和demethoxyfumitremorgin C，以及几种已知的二酮哌嗪类，如fumitremorgin C。化合物在微摩尔量级的剂量范围内抑制tsFT210细胞在G2或G2期的细胞周期进程。所获得的新天然产物的结构主要通过光谱学方法确定，特别是利用二维核磁共振光谱对其^1H和^<13>C核磁共振谱进行了详细分析。

Cancer cells are uncontrolled cells with deregulation of the cell cycle, therefore, new cell cycle inhibitors might be good candidates for caner chemotherapy and also be a source for providing moleclar probes useful in elucidating regulatory mechanism of the cell cycle.We have begun on the screening for new cell cycle inhibitors from microbial origin. During the screening, we have isolated novel diketopiperazine alkaloids, spirotryprostatins A,B,tryprostatins A,B and cyclotryprostatins B,D,together with three new natural diketopiperazines, cyclotryprostatins A,C and demethoxyfumitremorgin C,as well as several known diketopiperazines such as fumitremorgin C from the fermetation broth of a fungus, Aspergillus fumigatus BM939, through a separation procedure guided by inhibitory activity on the cell cycle progression of mouse tsFT210 cells. Compoiunds inhibited the cell cycle progression of tsFT210 cells at G2 or phase in the dose range of micromolar order.Strctures of the new natural products obtained were determined mainly by the use of spectroscopic methods especially by detailed analyzes of their ^1H and ^<13>C NMR spectra with the aid of 2D NMR spectroscopy.