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Correlating In Vitro Target-Oriented Screening and Docking: Inhibition of Matrix Metalloproteinases Activities by Flavonoids.

Authors
  • Crascì, Lucia1
  • Basile, Livia1
  • Panico, Annamaria1
  • Puglia, Carmelo1
  • Bonina, Francesco P1
  • Basile, Pierluigi Maria1
  • Rizza, Luisa2
  • Guccione, Salvatore1
  • 1 Dipartimento di Scienze del Farmaco, Università degli Studi di Catania, Catania, Italy. , (Italy)
  • 2 Bionap s. r. l., Contrada Fureria, Belpasso, Italy. , (Italy)
Type
Published Article
Journal
Planta Medica
Publisher
Georg Thieme Verlag KG
Publication Date
Jul 01, 2017
Volume
83
Issue
11
Pages
901–911
Identifiers
DOI: 10.1055/s-0043-104775
PMID: 28288492
Source
Medline
License
Unknown

Abstract

Metalloproteases are a family of zinc-containing endopeptidases involved in a variety of pathological disorders. The use of flavonoid derivatives as potential metalloprotease inhibitors has recently increased.Particular plants growing in Sicily are an excellent yielder of the flavonoids luteolin, apigenin, and their respective glycoside derivatives (7-O-rutinoside, 7-O-glucoside, and 7-O-glucuronide).The inhibitory activity of luteolin, apigenin, and their respective glycoside derivatives on the metalloproteases MMP-1, MMP-3, MMP-13, MMP-8, and MMP-9 was assessed and rationalized correlating in vitro target-oriented screening and in silico docking.The flavones apigenin, luteolin, and their respective glucosides have good ability to interact with metalloproteases and can also be lead compounds for further development. Glycones are more active on MMP-1, -3, -8, and -13 than MMP-9. Collagenases MMP-1, MMP-8, and MMP-13 are inhibited by compounds having rutinoside glycones. Apigenin and luteolin are inactive on MMP-1, -3, and -8, which can be interpreted as a better selectivity for both -9 and -13 peptidases. The more active compounds are apigenin-7-O-rutinoside on MMP-1 and luteolin-7-O-rutinoside on MMP-3. The lowest IC50 values were also found for apigenin-7-O-glucuronide, apigenin-7-O-rutinoside, and luteolin-7-O-glucuronide. The glycoside moiety might allow for a better anchoring to the active site of MMP-1, -3, -8, -9, and -13. Overall, the in silico data are substantially in agreement with the in vitro ones (fluorimetric assay).

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