Synthesis, in vitro and computational studies of 1,4-disubstituted 1,2,3-triazoles as potential α-glucosidase inhibitors

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Abstract

1,4-Disubstituted-1,2,3-triazoles were synthesized by Cu(I) catalyzed click reaction, where the azides, with electron donating and electron withdrawing groups acted as 1,3-dipoles and 1-ethynyl-1-cyclohexanol served as the terminal alkyne. These synthesized triazoles were subjected to enzymatic assay which showed promising activity against α-glucosidase; 1-(2-cyano-4-nitrophenyl)-4-(1-hydroxycyclohexyl)-1H-1,2,3-triazole 3m being the most active members of the library. Molecular docking studies of these triazoles with the homology-modeled α-glucosidase protein were also performed to delineate ligand-protein interactions at molecular level which suggested that Phe157, Arg312 and His279 are the major interacting residues in the biding site of the protein and may have a significant role in the inhibition of enzyme's function.

Original languageEnglish (US)
Pages (from-to)1029-38
Number of pages10
JournalBioorganic and Medicinal Chemistry Letters
Volume26
Issue number3
DOIs
StatePublished - Feb 1 2016

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Glucosidases
Triazoles
Cyclohexanols
Electrons
Proteins
Alkynes
Azides
Enzyme Assays
Libraries
Assays
Ligands
In Vitro Techniques
Enzymes

Keywords

  • Amino Acid Sequence
  • Bacillus cereus
  • Binding Sites
  • Catalytic Domain
  • Click Chemistry
  • Glycoside Hydrolase Inhibitors
  • Hydrogen Bonding
  • Molecular Docking Simulation
  • Molecular Sequence Data
  • Saccharomyces cerevisiae
  • Sequence Alignment
  • Structure-Activity Relationship
  • Triazoles
  • alpha-Glucosidases
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

@article{b538674f92c6403ca30672daf7113d27,
title = "Synthesis, in vitro and computational studies of 1,4-disubstituted 1,2,3-triazoles as potential α-glucosidase inhibitors",
abstract = "1,4-Disubstituted-1,2,3-triazoles were synthesized by Cu(I) catalyzed click reaction, where the azides, with electron donating and electron withdrawing groups acted as 1,3-dipoles and 1-ethynyl-1-cyclohexanol served as the terminal alkyne. These synthesized triazoles were subjected to enzymatic assay which showed promising activity against α-glucosidase; 1-(2-cyano-4-nitrophenyl)-4-(1-hydroxycyclohexyl)-1H-1,2,3-triazole 3m being the most active members of the library. Molecular docking studies of these triazoles with the homology-modeled α-glucosidase protein were also performed to delineate ligand-protein interactions at molecular level which suggested that Phe157, Arg312 and His279 are the major interacting residues in the biding site of the protein and may have a significant role in the inhibition of enzyme's function.",
keywords = "Amino Acid Sequence, Bacillus cereus, Binding Sites, Catalytic Domain, Click Chemistry, Glycoside Hydrolase Inhibitors, Hydrogen Bonding, Molecular Docking Simulation, Molecular Sequence Data, Saccharomyces cerevisiae, Sequence Alignment, Structure-Activity Relationship, Triazoles, alpha-Glucosidases, Journal Article, Research Support, Non-U.S. Gov't",
author = "Panda, {Siva S}",
note = "Copyright {\circledC} 2015 Elsevier Ltd. All rights reserved.",
year = "2016",
month = "2",
day = "1",
doi = "10.1016/j.bmcl.2015.12.033",
language = "English (US)",
volume = "26",
pages = "1029--38",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "3",

}

TY - JOUR

T1 - Synthesis, in vitro and computational studies of 1,4-disubstituted 1,2,3-triazoles as potential α-glucosidase inhibitors

AU - Panda, Siva S

N1 - Copyright © 2015 Elsevier Ltd. All rights reserved.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - 1,4-Disubstituted-1,2,3-triazoles were synthesized by Cu(I) catalyzed click reaction, where the azides, with electron donating and electron withdrawing groups acted as 1,3-dipoles and 1-ethynyl-1-cyclohexanol served as the terminal alkyne. These synthesized triazoles were subjected to enzymatic assay which showed promising activity against α-glucosidase; 1-(2-cyano-4-nitrophenyl)-4-(1-hydroxycyclohexyl)-1H-1,2,3-triazole 3m being the most active members of the library. Molecular docking studies of these triazoles with the homology-modeled α-glucosidase protein were also performed to delineate ligand-protein interactions at molecular level which suggested that Phe157, Arg312 and His279 are the major interacting residues in the biding site of the protein and may have a significant role in the inhibition of enzyme's function.

AB - 1,4-Disubstituted-1,2,3-triazoles were synthesized by Cu(I) catalyzed click reaction, where the azides, with electron donating and electron withdrawing groups acted as 1,3-dipoles and 1-ethynyl-1-cyclohexanol served as the terminal alkyne. These synthesized triazoles were subjected to enzymatic assay which showed promising activity against α-glucosidase; 1-(2-cyano-4-nitrophenyl)-4-(1-hydroxycyclohexyl)-1H-1,2,3-triazole 3m being the most active members of the library. Molecular docking studies of these triazoles with the homology-modeled α-glucosidase protein were also performed to delineate ligand-protein interactions at molecular level which suggested that Phe157, Arg312 and His279 are the major interacting residues in the biding site of the protein and may have a significant role in the inhibition of enzyme's function.

KW - Amino Acid Sequence

KW - Bacillus cereus

KW - Binding Sites

KW - Catalytic Domain

KW - Click Chemistry

KW - Glycoside Hydrolase Inhibitors

KW - Hydrogen Bonding

KW - Molecular Docking Simulation

KW - Molecular Sequence Data

KW - Saccharomyces cerevisiae

KW - Sequence Alignment

KW - Structure-Activity Relationship

KW - Triazoles

KW - alpha-Glucosidases

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.bmcl.2015.12.033

DO - 10.1016/j.bmcl.2015.12.033

M3 - Article

VL - 26

SP - 1029

EP - 1038

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 3

ER -