Aurones as New Porcine Pancreatic α-Amylase Inhibitors

Author(s): Khashayar Roshanzamir, Elaheh Kashani-Amin, Azadeh Ebrahim-Habibi*, Latifeh Navidpour*.

Journal Name: Letters in Drug Design & Discovery

Volume 16 , Issue 3 , 2019

Submit Manuscript
Submit Proposal

Graphical Abstract:


Abstract:

Background: Aurones, (Z)-2-benzylidenebenzofuran-3-one derivatives, are naturallyoccurring structural isomers of flavones, with promising pharmacological potential.

Methods: In this study, the structural requirements for the inhibition of porcine pancreatic α- amylase by hydroxylated or methoxylated aurone derivatives were investigated by assessing their in vitro biological activities against porcine pancreatic α-amylase.

Results: The structure-activity relationship of these inhibitors based on both in vitro and in silico findings showed that the hydrogen bonds between the OH groups of the A or B ring of (Z)- benzylidenebenzofuran-3-one derivatives and the catalytic residues of the binding site are crucial for their inhibitory activities.

Conclusion: It seems that the OH groups in aurones inhibit α-amylase in a manner similar to that of OH groups in flavones and flavonols.

Keywords: α-amylase, aurones, (Z)-2-arylidenebenzofuran-3-ones, isomers, methoxylated, flavonols.

[1]
Al-Kazaz, M.; Desseaux, V.; Marchis-Mouren, G.; Prodanov, E.; Santimone, M. The mechanism of porcine pancreatic alpha-amylase. Inhibition of maltopentaose hydrolysis by acarbose, maltose and maltotriose. Eur. J. Biochem., 1998, 252, 100-107.
[2]
Kim, M.J.; Lee, S.B.; Lee, H.S.; Lee, S.Y.; Baek, J.S.; Kim, D.; Moon, T.W.; Robyt, J.F.; Park, K.H. Comparative study of the inhibition of alpha-glucosidase, alpha-amylase, and cyclomaltodextrin glucanosyltransferase by acarbose, isoacarbose and acarviosineglucose. Arch. Biochem. Biophys., 1999, 371, 277-283.
[3]
Yamagishi, S.; Nakamura, K.; Takeuchi, M. Inhibition of postprandial hyperglycemia by acarbose is a promising therapeutic strategy for the treatment of patients with the metabolic syndrome. Med. Hypotheses, 2005, 65, 152-154.
[4]
Machius, M.; Vertesy, L.; Huber, R.; Wiegand, G. Carbohydrate and protein-based inhibitors of porcine pancreatic alpha amylase: Structure analysis and comparison of their binding characteristics. J. Mol. Biol., 1996, 260, 409-421.
[5]
Brayer, G.D.; Luo, Y.; Withers, S.G. The structure of human pancreatic alpha-amylase at 1.8 Å resolution and comparisons with related enzymes. Protein Sci., 1995, 4, 1730-1742.
[6]
Kotaru, M.; Iwami, K.; Yeh, H.Y.; Ibuki, F. In vivo action of alpha-amylase inhibitor from cranberry bean (Phaseolus vulgaris) in rat small intestine. J. Nutr. Sci. Vitaminol. , 1989, 35, 579-588.
[7]
Tadera, K.; Minami, Y.; Takamatsu, K.; Matsuoka, T. Inhibition of alpha-glucosidase and alpha-amylase by flavonoids. J. Nutr. Sci. Vitaminol. , 2006, 52, 149-153.
[8]
Lo-Piparo, E.; Scheib, H.; Frei, N.; Williamson, G.; Grigorov, M.; Chou, C.J. Flavonoids for controlling starch digestion: Structural requirements for inhibiting human alpha-amylase. J. Med. Chem., 2008, 51, 3555-3561.
[9]
Harborne, J.B.; Williams, C.A. Advances in flavonoid research since 1992. Phytochemistry, 2000, 55, 481-504.
[10]
Sato, T.; Nakayama, T.; Kikuchi, S.; Fukui, Y.; Yonekura-Sakakibara, K.; Ueda, T.; Nishino, T.; Tanaka, Y.; Kusumi, T. Enzymatic formation of aurones in the extracts of yellow snapdragon flowers. Plant Sci., 2001, 160, 229-236.
[11]
Westenburg, H.E.; Lee, K.J.; Lee, S.K.; Fong, H.H.S.; VanBreemen, R.B.; Pezzuto, J.M.; Kinghorn, A.D. Activity-guided isolation of antioxidative constituents of cotinus coggygria. J. Nat. Prod., 2000, 63, 1696-1698.
[12]
Nakayama, T.; Sato, T.; Fukui, Y.; Yonekura-Sakakibara, K.; Hayashi, H.; Tanaka, Y.; Kusumi, T.; Nishino, T. Specificity analysis and mechanism of aurone synthesis catalyzed by aureusidin synthase, a polyphenol oxidase homolog responsible for flower coloration. FEBS Lett., 2001, 499, 107-111.
[13]
Nakayama, T.; Yonekura-Sakakibara, K.; Sato, T.; Kikuchi, S.; Fukui, Y.; Fukuchi-Mizutani, M.; Ueda, T.; Nakao, M.; Tanaka, Y.; Kusumi, T.; Nishino, T. Aureusidin synthase: A polyphenol oxidase homolog responsible for flower coloration. Science, 2000, 290, 1163-1166.
[14]
Shrestha, S.; Natarajan, S.; Park, J-H.; Lee, D-Y.; Cho, J-G.; Kim, G-S.; Jeon, Y-J.; Yeon, S-W.; Yang, D-C.; Baek, N-I. Potential neuroprotective flavonoid-based inhibitors of CDK5/p25 from Rhus parviflora. Bioorg. Med. Chem. Lett., 2013, 23, 5150-5154.
[15]
Venkateswarlu, S.; Murty, G.N.; Satyanarayana, M. “On water” synthesis of aurones: First synthesis of 4,5,3′,4′,5′-pentamethoxy-6-hydroxyaurone from Smilax riparia. Arkivoc, 2017, 2017, 303-314.
[16]
Park, H.S.; Nelson, D.E.; Taylor, Z.E.; Hayes, J.B.; Cunningham, K.D.; Arivett, B.A.; Ghosh, R.; Wolf, L.C.; Taylor, K.M.; Farone, M.B.; Handy, S.T.; Farone, A.L. Suppression of LPS-induced NF-κB activity in macrophages by the synthetic aurone, (Z)-2-((5-(hydroxymethyl)furan-2-yl)methylene)benzofuran-3(2H)-one. Int. Immunopharmacol., 2017, 43, 116-128.
[17]
Kadayat, T.M.; Banskota, S.; Gurung, P.; Bist, G.; Thapa, M.T.B.; Shrestha, A.; Kim, J-A.; Lee, E-S. Discovery and structure-activity relationship studies of 2-benzylidene-2,3-dihydro-1H-inden-1-one and benzofuran-3(2H)-one derivatives as a novel class of potential therapeutics for inflammatory bowel disease. European . J. Med. Chem., 2017, 137, 575-597.
[18]
Wang, S.; Xu, L.; Lu, Y-T.; Liu, Y-F.; Han, B.; Liu, T.; Tang, J.; Li, J.; Wu, J.; Li, J-Y.; Yu, L-F.; Yang, F. Discovery of benzofuran-3(2H)-one derivatives as novel DRAK2 inhibitors that protect islet β-cells from apoptosis. European . J. Med. Chem., 2017, 130, 195-208.
[19]
Fitzgerald, D.M. OʹSullivan, J.F.; Philbin, E.M.; Wheeler, T.S. Ring expansion of 2-benzylidenecoumaran-3-ones-a synthesis of flavones. J. Chem. Soc., 1955, 860-862.
[20]
Lee, C-Y.; Chew, E-H.; Go, M-L. Functionalized aurones as inducers of NAD(P)H:quinine oxidoreductase 1 that activate AhR/XRE and Nrf2/ARE signaling pathways: Synthesis, evaluation and SAR. European . J. Med. Chem., 2010, 45, 2957-2971.
[21]
Detsi, A.; Majdalani, M.; Kontogiorgis, C.A.; Hadjipavlou-Litina, D.; Kefalas, P. Natural and synthetic 2ʹ-hydroxy-chalcones and aurones: Synthesis, characterization and evaluation of the antioxidant and soybean lipooxygenase inhibitory activity. Bioorg. Med. Chem., 2009, 17, 8073-8085.
[22]
Bernfeld, P. Alpha- and beta-amylases. Methods Enzymol., 1955, 1, 149-154.
[23]
MOE Chemical Computing Group Inc., Montreal, Quebec, Canada, 2012. 10, see. http://www.chemcomp.com
[24]
Navidpour, L.; Shadnia, H.; Shafaroodi, H.; Amini, M.; Dehpour, A.R.; Shafiee, A. Design, synthesis, and biological evaluation of substituted 2-alkylthio-1,5-diarylimidazoles as selective COX-2 inhibitors. Bioorg. Med. Chem., 2007, 15, 1976-1982.
[25]
Wright, J.S.; Shadnia, H.; Anderson, J.M.; Durst, T.; Asim, M.; El-Salfiti, M.; Choueiri, C.; Pratt, M.A.C.; Ruddy, S.C.; Lau, R.; Carlson, K.E.; Katzenellenbogen, J.A.; O’Brien, P.J.; Wan, L. A-CD estrogens. I. Substituent effects, hormone potency, and receptor subtype selectivity in a new family of flexible estrogenic compounds. J. Med. Chem., 2011, 54, 433-448.
[26]
PDB-THAW 1.0, 2009, functional source code freely available from http://www.shadnia.com/H_Thaw/
[27]
Halgren, T.A. MMFF VI. MMFF94s option for energy minimization studies. J. Comp. Chem., 1999, 20, 720-729.
[28]
Halgren, T.A. MMFF VII. Characterization of MMFF94, MMFF94s, and other widely available force fields for conformational energies and for intermolecular-interaction energies and geometries. J. Comp. Chem., 1999, 20, 730-748.
[29]
Bashford, D.; Case, D. Generalized born models of macromolecular solvation effects. Annu. Rev. Phys. Chem., 2000, 51, 129-152.
[30]
Boumendjel, A.; Fortune, A.; Haudecoeur, R.; Nicolle, E.; Yi, W.; Ahmed-Belkacem, A.; Brillet, R.; Pallier, C.; Pawlotsky, J.M.; Belle, C. Discovery of naturally occurring aurones that are potent allosteric inhibitors of hepatitis C virus RNA-dependent RNA polymerase. J. Med. Chem., 2011, 54, 5395-54021.
[31]
Thomas, M.G.; Lawson, C.; Allanson, N.M.; Leslie, B.W.; Bottomley, J.R.; McBride, A.; Olusanya, O.A. A Series of (Z)-2-Benzylidene-6,7-dihydroxybenzofuran-3[2H]-ones as Inhibitors of Chorismate Synthase. Bioorg. Med. Chem. Lett., 2003, 13, 423-426.
[32]
Najafian, M.; Ebrahim-Habibi, A.; Hezareh, N.; Yaghmaei, P.; Parivar, K.; Larijani, B. Trans-chalcone: A novel small molecule inhibitor of mammalian alpha-amylase. Mol. Biol. Rep., 2011, 38, 1617-1620.
[33]
Williams, L.K.; Li, C.; Withers, S.G.; Brayer, G.D. Order and disorder: Differential structural impacts of myricetin and ethyl caffeate on human amylase, an antidiabetic target. J. Med. Chem., 2012, 55, 10177-10186.


Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 16
ISSUE: 3
Year: 2019
Page: [333 - 340]
Pages: 8
DOI: 10.2174/1570180815666180712150600
Price: $58

Article Metrics

PDF: 14
HTML: 3