Molecular Biology Reports

, Volume 38, Issue 3, pp 1617–1620

Trans-chalcone: a novel small molecule inhibitor of mammalian alpha-amylase

  • Mahmoud Najafian
  • Azadeh Ebrahim-Habibi
  • Nastaran Hezareh
  • Parichehreh Yaghmaei
  • Kazem Parivar
  • Bagher Larijani


Trans-chalcone (1,3-diphenyl-2-propen-1-one), a biphenolic core structure of flavonoids precursor was tested for inhibitory activity toward alpha-amylase. Porcine pancreatic alpha-amylase was observed to be effectively inhibited by this compound, which showed competitive behavior with a Ki of 48 μM. Soluble starch (the natural substrate of the enzyme) was used in this study in order to obtain more realistic results. The possible binding mode of the compound was assessed in silico, and the two residues Trp59, and Tyr62 were proposed as main interacting residues with trans-chalcone. In conclusion, this compound could be used to design effective inhibitors of alpha-amylase.


Trans-chalcone 1,3-Diphenyl-2-propen-1-one Alpha-amylase Inhibitor Diabetes 


  1. 1.
    Machius M, Vertesy L, Huber R, Wiegand G (1996) Carbohydrate and protein-based inhibitors of porcine pancreatic alpha-amylase: structure analysis and comparison of their binding characteristics. J Mol Biol 260:409–421CrossRefPubMedGoogle Scholar
  2. 2.
    Franco OL, Rigden DJ, Melo FR, Grossi-De-Sa MF (2002) Plant alpha-amylase inhibitors and their interaction with insect alpha-amylases. Eur J Biochem 269:397–412CrossRefPubMedGoogle Scholar
  3. 3.
    Nahoum V, Roux G, Anton V, Rouge P, Puigserver A, Bischoff H, Henrissat B, Payan F (2000) Crystal structures of human pancreatic alpha-amylase in complex with carbohydrate and proteinaceous inhibitors. Biochem J 346(Pt 1):201–208CrossRefPubMedGoogle Scholar
  4. 4.
    Kotaru M, Iwami K, Yeh HY, Ibuki F (1989) In vivo action of alpha-amylase inhibitor from cranberry bean (Phaseolus vulgaris) in rat small intestine. J Nutr Sci Vitaminol (Tokyo) 35:579–588Google Scholar
  5. 5.
    Ali H, Houghton PJ, Soumyanath A (2006) Alpha-amylase inhibitory activity of some Malaysian plants used to treat diabetes; with particular reference to Phyllanthus amarus. J Ethnopharmacol 107:449–455CrossRefPubMedGoogle Scholar
  6. 6.
    Teixeira VL, Rocha FD, Houghton PJ, Kaplan MA, Pereira RC (2007) Alpha-amylase inhibitors from Brazilian seaweeds and their hypoglycemic potential. Fitoterapia 78:35–36CrossRefPubMedGoogle Scholar
  7. 7.
    Yokose K, Ogawa K, Sano T, Watanabe K, Maruyama HB, Suhara Y (1983) New alpha-amylase inhibitor, trestatins I. Isolation, characterization and biological activities of trestatins A, B and C. J Antibiot (Tokyo) 36:1157–1165Google Scholar
  8. 8.
    Yamagishi S, Nakamura K, Takeuchi M (2005) Inhibition of postprandial hyperglycemia by acarbose is a promising therapeutic strategy for the treatment of patients with the metabolic syndrome. Med Hypotheses 65:152–154CrossRefPubMedGoogle Scholar
  9. 9.
    Miura T, Koide T, Ohichi R, Kako M, Usami M, Ishihara E, Yasuda N, Ishida H, Seino Y, Tanigawa K (1998) Effect of acarbose (alpha-glucosidase inhibitor) on disaccharase activity in small intestine in KK-Ay and ddY mice. J Nutr Sci Vitaminol (Tokyo) 44:371–379Google Scholar
  10. 10.
    Hanefeld M (1998) The role of acarbose in the treatment of non-insulin-dependent diabetes mellitus. J Diabetes Complications 12:228–237CrossRefPubMedGoogle Scholar
  11. 11.
    Boivin M, Flourie B, Rizza RA, Go VL, DiMagno EP (1988) Gastrointestinal and metabolic effects of amylase inhibition in diabetics. Gastroenterology 94:387–394PubMedGoogle Scholar
  12. 12.
    Lo Piparo E, Scheib H, Frei N, Williamson G, Grigorov M, Chou CJ (2008) Flavonoids for controlling starch digestion: structural requirements for inhibiting human alpha-amylase. J Med Chem 51:3555–3561CrossRefPubMedGoogle Scholar
  13. 13.
    Ferrer JL, Austin MB, Stewart C Jr, Noel JP (2008) Structure and function of enzymes involved in the biosynthesis of phenylpropanoids. Plant Physiol Biochem 46:356–370CrossRefPubMedGoogle Scholar
  14. 14.
    Bernfeld P (1955) Alpha- and beta-amylases. Methods Enzymol 1:149–154CrossRefGoogle Scholar
  15. 15.
    Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31:455–461PubMedGoogle Scholar
  16. 16.
    Tadera K, Minami Y, Takamatsu K, Matsuoka T (2006) Inhibition of alpha-glucosidase and alpha-amylase by flavonoids. J Nutr Sci Vitaminol (Tokyo) 52:149–153CrossRefGoogle Scholar
  17. 17.
    Tarling CA, Woods K, Zhang R, Brastianos HC, Brayer GD, Andersen RJ, Withers SG (2008) The search for novel human pancreatic alpha-amylase inhibitors: high-throughput screening of terrestrial and marine natural product extracts. Chembiochem 9:433–438CrossRefPubMedGoogle Scholar
  18. 18.
    Ebrahim-Habibi A (2008) Flavonoids as potential antihyperglycemics: an in silico study of their alpha-amylase inhibitory mode. Drugs Future 33(Suppl.A):306–307Google Scholar
  19. 19.
    Ramasubbu N, Ragunath C, Mishra PJ, Thomas LM, Gyemant G, Kandra L (2004) Human salivary alpha-amylase Trp58 situated at subsite −2 is critical for enzyme activity. Eur J Biochem 271:2517–2529CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Mahmoud Najafian
    • 1
  • Azadeh Ebrahim-Habibi
    • 2
  • Nastaran Hezareh
    • 2
  • Parichehreh Yaghmaei
    • 1
  • Kazem Parivar
    • 1
  • Bagher Larijani
    • 2
  1. 1.Science and Research Branch Islamic Azad UniversityTehranIran
  2. 2.Endocrinology and Metabolism Research CenterTehran University of Medical SciencesTehranIran

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