A novel 15-spiro diterpenoid dimer from Andrographis paniculata with inhibitory potential against human carboxylesterase 2

Bioorg Chem. 2020 Apr:97:103680. doi: 10.1016/j.bioorg.2020.103680. Epub 2020 Feb 20.

Abstract

The phytochemical investigation of Andrographis paniculata resulted in the isolation of a novel 15-spiro diterpenoid dimer bisandrographolide G (1). Its structure was determined by 1D and 2D NMR, HRESIMS, electronic circular dichroism (ECD), and TD DFT calculations of ECD spectra. It showed potent inhibitory activity against human carboxylesterase 2 (CES 2) with an IC50 value of 4.61 ± 0.23 μM, and it was defined as a mixed-competitive type inhibitor with a Ki value of 8.88 μM based on the inhibition kinetics result. This finding gave us a hit to develop new generation of human CES 2 inhibitors.

Keywords: Andrographis paniculata; Diterpenoid dimer; Human carboxylesterase 2; Kinetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Andrographis / chemistry*
  • Carboxylesterase / antagonists & inhibitors*
  • Carboxylesterase / metabolism
  • Diterpenes / chemistry*
  • Diterpenes / pharmacology*
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Models, Molecular
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology

Substances

  • Diterpenes
  • Enzyme Inhibitors
  • Spiro Compounds
  • CES2 protein, human
  • Carboxylesterase