Novel mammalian cell cycle inhibitors, cyclotroprostatins A–D, produced by Aspergillus fumigatus, which inhibit mammalian cell cycle at G2/M phase

Abstract

Four new natural diketopiperazine derivatives, cyclotryprostatins A (1), B (2), C (3) and D (4), were isolated as new inhibitors of the mammalian cell cycle from the secondary metabolites of Aspergillus fumigatus BM939 through a separation procedure guided by cell cycle inhibitory activity. The structures of 1-4 were determined by spectroscopic methods especially by detailed analysis of their 1H and 13C NMR spectra with the aid of 2D NMR techniques. Compounds 1-4 inhibited the cell cycle progression of tsFT210 cells at the G2/M phase with IC50 values of 5.6 μM (1), 19.5 μM (2), 23.4 μM (3) and 25.3 μM (4), respectively.