New triazinoindole bearing thiazole/oxazole analogues: Synthesis, α-amylase inhibitory potential and molecular docking study

Bioorg Chem. 2019 Nov:92:103284. doi: 10.1016/j.bioorg.2019.103284. Epub 2019 Sep 17.

Abstract

New triazinoindole bearing thiazole/oxazole analogues (1-21) were synthesized and characterized through spectroscopic techniques such as HREI-MS, 1H and 13C NMR. The configuration of compound 2i and 2k was confirmed through NOESY. All analogues were evaluated against α-amylase inhibitory potential. Among the synthesized analogues, compound 1h, 1i, 1j, 2a and 2f having IC50 values 1.80 ± 0.20, 1.90 ± 0.30, 1.2 ± 0.30, 1.2 ± 0.01 and 1.30 ± 0.20 μM respectively, showed excellent α-amylase inhibitory potential when compared with acarbose as standard (IC50 = 0.91 ± 0.20 µM). All other analogues showed good to moderate inhibitory potential. Structural activity relationship (SAR) has been established and binding interactions were confirmed through docking studies.

Keywords: Molecular docking; Oxazole; SAR; Synthesis; Thiazole; Triazinoindole; α-amylase.

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*
  • Humans
  • Molecular Docking Simulation*
  • Molecular Structure
  • Oxazoles / chemistry
  • Oxazoles / pharmacology*
  • Structure-Activity Relationship
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*
  • Triazines / chemical synthesis
  • Triazines / chemistry
  • Triazines / pharmacology*
  • alpha-Amylases / antagonists & inhibitors*
  • alpha-Amylases / metabolism

Substances

  • Glycoside Hydrolase Inhibitors
  • Oxazoles
  • Thiazoles
  • Triazines
  • alpha-Amylases