Novel Mammalian Cell Cycle Inhibitors, Tryprostatins A, B and Other Diketopiperazines Produced by Aspergillus fumigatus. I. Taxonomy, Fermentation, Isolation and Biological Properties.

• DOI: 10.7164/antibiotics.49.527
• Publication Date: 2012-02-29T22:45:19Z
• Authors: CHENG-BIN CUI; HIDEAKI KAKEYA; GEN OKADA; RIE ONOSE; HIROYUKI OSADA
• Keywords: Mice; Indoles; Aspergillus fumigatus; Cell Cycle; Fermentation; Animals; Protein Kinases; 01 natural sciences; Piperazines; Indole Alkaloids; 0104 chemical sciences

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.