Identification of small molecules inhibitors of GCN5 histone acetyltransferase activity

Mai, Antonello; Rotili, Dante; Ornaghi, P; Tosi, F; Vicidomini, C; Sbardella, G; Nebbioso, A; Altucci, L; Filetici, P.

Starting from a yeast phenotypic screening performed on 21 chemically different substances we described the discovery of two small molecules as GCN5 inhibitors. The 2-methyl-3-carbethoxyquinoline 9 and its 2-desmethyl analogue 18 were able to significantly reduce the yeast cell growth, thus miming the effect of GCN5 deletion mutant. Tested to evaluate their effect on GCN5-dependent transcription of the HIS3 gene, 9 and 18 showed high inhibitory activity of gene transcription, more evident in activated conditions. Compound 9 was also able to reduce the acetylation levels of H3 and, to a lesser extent, H4 in yeast at 0.6 mM. In human leukemia U937 cells, at 1 mM concentration 9 showed 27% apoptosis induction, while 18 had just a little effect in the same conditions. Further studies on 9 and 18 will be performed to deepen their effects on GCN5-related phenomena.

Identification of small molecules inhibitors of GCN5 histone acetyltransferase activity / Mai, Antonello; Rotili, Dante; Ornaghi, P; Tosi, F; Vicidomini, C; Sbardella, G; Nebbioso, A; Altucci, L; Filetici, P.. - In: ARKIVOC. - ISSN 1551-7004. - 8(2006), pp. 24-37.

Titolo:	Identification of small molecules inhibitors of GCN5 histone acetyltransferase activity
Autori:	MAI, Antonello ROTILI, Dante ORNAGHI P TOSI F VICIDOMINI C SBARDELLA G NEBBIOSO A ALTUCCI L FILETICI P. mostra contributor esterni nascondi contributor esterni
Data di pubblicazione:	2006
Rivista:	ARKIVOC
Citazione:	Identification of small molecules inhibitors of GCN5 histone acetyltransferase activity / Mai, Antonello; Rotili, Dante; Ornaghi, P; Tosi, F; Vicidomini, C; Sbardella, G; Nebbioso, A; Altucci, L; Filetici, P.. - In: ARKIVOC. - ISSN 1551-7004. - 8(2006), pp. 24-37.
Handle:	http://hdl.handle.net/11573/12854
Appartiene alla tipologia:	01a Articolo in rivista

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