Evaluation of 2-indolcarbohydrazones as potent α-glucosidase inhibitors, in silico studies and DFT based stereochemical predictions

Bioorg Chem. 2015 Dec:63:24-35. doi: 10.1016/j.bioorg.2015.09.001. Epub 2015 Sep 10.

Abstract

2-Indolcarbohydrazones 1-28 were synthesized and evaluated for their α-glucosidase inhibitory potential. A varying degree of inhibitory potential with IC50 values in the range of 2.3±0.11-226.4±6.8μM was observed while comparing these outcomes with the standard acarbose (IC50=906.0±6.3μM). The stereochemistry of ten (10) randomly selected compounds (1, 3, 6, 8, 12, 18, 19, 23, 25 and 28) was predicted by Density Functional Theory (DFT). The stability of E isomer was deduced by comparing the calculated and experimental vibration modes of νCO, νNC and νCH (CH in NCH-R). It was observed that except compound 18, all other compounds were deduced to have E configuration while molecular modeling studies revealed the key interactions between enzyme and synthesized compounds.

Keywords: 2-Indolcarbohydrazones; Density Functional Theory (DFT); In silico studies; Structure–activity relationship; α-Glucosidase inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Glycoside Hydrolase Inhibitors / chemical synthesis
  • Glycoside Hydrolase Inhibitors / chemistry
  • Glycoside Hydrolase Inhibitors / pharmacology*
  • Hydrazones / chemical synthesis
  • Hydrazones / chemistry
  • Hydrazones / pharmacology*
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Molecular Docking Simulation
  • Molecular Structure
  • Quantum Theory*
  • Saccharomyces cerevisiae / enzymology
  • Stereoisomerism
  • Structure-Activity Relationship
  • alpha-Glucosidases / metabolism*

Substances

  • 2-indolcarbohydrazone
  • Glycoside Hydrolase Inhibitors
  • Hydrazones
  • Indoles
  • alpha-Glucosidases