A structure-activity study for the inhibition of metalloproteinase-9 activity and gene expression by analogues of gallocatechin-3-gallate

M. Dell'Agli, S. Bellosta, L. Rizzi, G. V. Galli, M. Canavesi, F. Rota, R. Parente, E. Bosisio, S. Romeo

Research output: Contribution to journalArticle

Abstract

Catechins are able to modulate the gelatinolytic activity of matrix metalloproteinase-9 (MMP-9) by reducing its release from macrophages. Gallocatechins decrease MMP-9 secretion 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 testing the effect of analogues of (±)-gallocatechin-3-gallate (±)-GCG, selectively deprived of hydroxyl groups, on MMP-9 activity, transcription, and secretion. Our results indicate that (±)-GCG and (±)-catechin-3-gallate are characterized by a substitution pattern compatible with direct inhibition of MMP-9 activity. Conversely, when transcription was the target, (±)-trans-3-flavanol-3- benzoate, lacking all the hydroxyl groups, was the most effective both in lowering MMP-9 promoter activity and consequently protein secretion, and in inhibiting nuclear-factor-κB-driven transcription. Our results suggest that the structural requirements for enzyme inhibition are different from those necessary for targeting gene expression.

Original languageEnglish
Pages (from-to)2896-2903
Number of pages8
JournalCellular and Molecular Life Sciences
Volume62
Issue number23
DOIs
Publication statusPublished - Dec 2005

Keywords

  • Catechins
  • Gallocatechin-3-gallate
  • Gelatinase B
  • Gene expression
  • Matrix metalloproteinase-9
  • NF-κB driven-transcription
  • Structure-activity relationship

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

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    Dell'Agli, M., Bellosta, S., Rizzi, L., Galli, G. V., Canavesi, M., Rota, F., Parente, R., Bosisio, E., & Romeo, S. (2005). A structure-activity study for the inhibition of metalloproteinase-9 activity and gene expression by analogues of gallocatechin-3-gallate. Cellular and Molecular Life Sciences, 62(23), 2896-2903. https://doi.org/10.1007/s00018-005-5422-7