NOVEL MAMMALIAN-CELL CYCLE INHIBITORS, CYCLOTRYPROSTATINS A-D, PRODUCED BY ASPERGILLUS-FUMIGATUS, WHICH INHIBIT MAMMALIAN-CELL CYCLE AT G2 M PHASE/

Four new natural diketopiperazine derivatives, cyclotryprostatins A (1 ), B (2), C (3) and D (4), were isolated as new inhibitors of the mamm alian cell cycle from the secondary metabolites of Aspergillus fumigat us BM939 through a separation procedure guided by cell cycle inhibitor y activity. The structures of 1-4 were determined by spectroscopic met hods especially by detailed analyses of their H-1 and C-13 NMR spectra with the id of 2D NMR techniques. Compounds 1-4 inhibited the cell cy cle progression of tsFT210 cells at the G2/M phase with IC50 values of 5.6 mu M (1), 19.5 mu M (2), 23.4 mu M (3) and 25.3 mu M (4), respect ively. Copyright (C) 1996 Elsevier Science Ltd