Development of bioprobes which regulate mammalian cell cycle

点击翻译按钮获取中文摘要

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.