Novel mammalian cell cycle inhibitors, tryprostatins A, B and other diketopiperazines produced by Aspergillus fumigatus. I. Taxonomy, fermentation, isolation and biological properties.
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.
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C B
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Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.
Kakeya
H
H
Okada
G
G
Onose
R
R
Osada
H
H
D000818:Animals; D001232:Aspergillus fumigatus; D002453:Cell Cycle / Q000187:drug effects; D005285:Fermentation; D026121:Indole Alkaloids; D007211:Indoles / Q000302:isolation & purification* / Q000494:pharmacology; D051379:Mice; D010879:Piperazines / Q000302:isolation & purification* / Q000494:pharmacology; D011494:Protein Kinases / Q000187:drug effects
D026121:Indole Alkaloids; D007211:Indoles; D010879:Piperazines; C100698:demethoxyfumitremorgin C; C097858:tryprostatin A; C097859:tryprostatin B; D011494:Protein Kinases