A structure-activity study for the inhibition of metalloprotease-9 activity and gene expression by analogues of gallocatechin-3-gallate
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Data di Pubblicazione:
2006
Citazione:
A structure-activity study for the inhibition of metalloprotease-9 activity and gene expression by analogues of gallocatechin-3-gallate / S. Bellosta, M. Dell'Agli, L. Rizzi, G.V. Galli, M. Canavesi, F. Rota, R. Parente, E. Bosisio, S. Romeo. ((Intervento presentato al 14. convegno International Symposium on Atherosclerosis tenutosi a Roma nel 2006.
Abstract:
Catechins modulate the gelatinolytic activity of matrix metalloproteinase-9 (MMP-9) by reducing its release from macrophages and by lowering MMP-9 promoter activity and mRNA levels. The effect appears to be dependent on some structural and stereochemical requirements. In this study, the relationship between chemical structure and activity was studied by synthesizing analogues of (-t-)-gallocatechin-3-gallate selectively deprived of hydroxyl groups. The
compounds were added to murine macrophages at concentrations ranging from 1 to 30 uM, and the effect on MMP-9 activity, transcription, and secretion
was measured by standard techniques. Our results indicate that the compound containing all the hydroxyl groups was the most effective in inhibiting directly
MMP-9 activity (80% inhibition, p<0.001), and this inhibitory effect decreased with the increasing of hydroxyl groups number. Conversely, when
transcription was the target, (-t-)-trans-3-flavanol-3-benzoate, lacking all the hydroxyl groups, was the most effective both in lowering MMP-9 promoter
activity (62%, p<0.001) and consequently protein secretion (68%, p<0.001) and in inhibiting nucleax-factor-kB-driven transcription (72%, p<0.001). The
results of the present study supply new insights on how catechin derivatives can act at the transcriptional or at enzyme level, indicating that the structural
features required for the enzymatic inhibition are different from those necessaxy for the down regulation of gene expression. These data may provide new tools for designing potent and selective agents for the modulation of MMP-9 activity and gene expression.
Tipologia IRIS:
14 - Intervento a convegno non pubblicato
Elenco autori:
S. Bellosta, M. Dell'Agli, L. Rizzi, G.V. Galli, M. Canavesi, F. Rota, R. Parente, E. Bosisio, S. Romeo
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