Phytochemicals with NO inhibitory effects and interactions with iNOS protein from Trigonostemon howii

Bioorg Chem. 2017 Dec:75:71-77. doi: 10.1016/j.bioorg.2017.08.008. Epub 2017 Aug 24.

Abstract

A phytochemical investigation to obtain new NO inhibitors led to the isolation of nine compounds including one new guaiane-type sesquiterpenoid (1) and two new cleistanthane diterpenoids (2 and 3) from the stems of Trigonostemon howii. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of new compounds 1-3 were established via comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 2 and 3 possess a rare 3,4-seco-cleistanthane diterpenoid skeleton. All of the compounds showed inhibitory effects on lipopolysaccharide-induced NO production in murine microglial BV-2 cells. The further molecular docking studies indicated the strong interactions between some bioactive compounds with the iNOS protein, which revealed the possible and potential mechanism of NO inhibition of bioactive compounds.

Keywords: Cleistanthane diterpenoid; Molecular docking; NO inhibitory activities; TDDFT ECD calculations; Trigonostemon howii; iNOS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Catalytic Domain
  • Circular Dichroism
  • Diterpenes / chemistry
  • Diterpenes / isolation & purification*
  • Diterpenes / pharmacology*
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism
  • Euphorbiaceae / chemistry*
  • Euphorbiaceae / metabolism
  • Magnetic Resonance Spectroscopy
  • Molecular Conformation
  • Molecular Docking Simulation
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II / metabolism
  • Phytochemicals / chemistry*
  • Phytochemicals / metabolism
  • Plant Stems / chemistry
  • Plant Stems / metabolism
  • Sesquiterpenes, Guaiane / chemistry
  • Sesquiterpenes, Guaiane / isolation & purification*
  • Sesquiterpenes, Guaiane / pharmacology*
  • Thermodynamics

Substances

  • Diterpenes
  • Enzyme Inhibitors
  • Phytochemicals
  • Sesquiterpenes, Guaiane
  • howpene A
  • howpene B
  • howpene C
  • Nitric Oxide
  • Nitric Oxide Synthase Type II