To improve the current understanding of the role of stilbenoids in the management of diabetes, the inhibition of the pancreatic α-amylase by resveratrol derivatives was investigated. To approach in a systematic way, the mechanistic and structural aspects of the interaction, potential bioactive agents were prepared as single molecules, that were used for the biological evaluation of the determinants of inhibitory binding. Some dimeric stilbenoids—in particular, viniferin isomers— were found to be better than the reference drug acarbose in inhibiting the pancreatic α-amylase. Racemic mixtures of viniferins were more effective inhibitors than the respective isolated pure enantiomers at an equivalent total concentration, and displayed cooperative effects not observed with the individual enantiomers. The molecular docking analysis provided a thermodynamics-based rationale for the measured inhibitory ability and for the observed synergistic effects. Indeed, the binding of additional ligands on the surface of the alpha-amylase was found to decrease the dissociation constant of inhibitors bound to the active site of the enzyme, thus providing a mechanistic rationale for the observed inhibitory synergies.

Inhibition of Pancreatic α-amylase by Resveratrol Derivatives : Biological Activity and Molecular Modelling Evidence for Cooperativity between Viniferin Enantiomers / L.M. Mattio, M. Marengo, C. Parravicini, I. Eberini, S. Dallavalle, F. Bonomi, S. Iametti, A. Pinto. - In: MOLECULES. - ISSN 1420-3049. - 24:18(2019 Sep 05), pp. 3225.1-3225.14. [10.3390/molecules24183225]

Inhibition of Pancreatic α-amylase by Resveratrol Derivatives : Biological Activity and Molecular Modelling Evidence for Cooperativity between Viniferin Enantiomers

L.M. Mattio
Primo
;
M. Marengo;C. Parravicini;I. Eberini;S.M.D. Dallavalle;F. Bonomi;S. Iametti;A. Pinto
2019

Abstract

To improve the current understanding of the role of stilbenoids in the management of diabetes, the inhibition of the pancreatic α-amylase by resveratrol derivatives was investigated. To approach in a systematic way, the mechanistic and structural aspects of the interaction, potential bioactive agents were prepared as single molecules, that were used for the biological evaluation of the determinants of inhibitory binding. Some dimeric stilbenoids—in particular, viniferin isomers— were found to be better than the reference drug acarbose in inhibiting the pancreatic α-amylase. Racemic mixtures of viniferins were more effective inhibitors than the respective isolated pure enantiomers at an equivalent total concentration, and displayed cooperative effects not observed with the individual enantiomers. The molecular docking analysis provided a thermodynamics-based rationale for the measured inhibitory ability and for the observed synergistic effects. Indeed, the binding of additional ligands on the surface of the alpha-amylase was found to decrease the dissociation constant of inhibitors bound to the active site of the enzyme, thus providing a mechanistic rationale for the observed inhibitory synergies.
resveratrol; stilbenoids; pancreatic alpha-amylase; enzyme inhibition; molecular docking; food bioactives synergism
Settore CHIM/08 - Chimica Farmaceutica
Settore BIO/10 - Biochimica
Settore CHIM/10 - Chimica degli Alimenti
   PIANO DI SOSTEGNO ALLA RICERCA 2015-2017 - LINEA 2 "DOTAZIONE ANNUALE PER ATTIVITA' ISTITUZIONALE"
   UNIVERSITA' DEGLI STUDI DI MILANO

   Dipartimenti di Eccellenza 2018-2022 - Dipartimento di SCIENZE FARMACOLOGICHE E BIOMOLECOLARI
   MINISTERO DELL'ISTRUZIONE E DEL MERITO

   Fondo per il finanziamento delle attività base di ricerca - DIPARTIMENTO DI SCIENZE PER GLI ALIMENTI, LA NUTRIZIONE E L'AMBIENTE
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
5-set-2019
Article (author)
File in questo prodotto:
File Dimensione Formato  
molecules-24-03225.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 5.77 MB
Formato Adobe PDF
5.77 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/683821
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 26
  • ???jsp.display-item.citation.isi??? 22
social impact