Tulipaline A: structure-activity aspects as a nematicide and V-ATPase inhibitor

Pestic Biochem Physiol. 2014 Jun:112:33-9. doi: 10.1016/j.pestbp.2014.05.002. Epub 2014 May 23.

Abstract

Carbonyl groups are known to form covalent adducts with endogenous proteins, but so far, their nematicidal mechanism of action of has been overlooked. The nematicidal activity of ten lactones was tested in vitro against the root knot nematodes Meloidogyne incognita and Meloidogynearenaria. In particular, the saturated lactones α-methylene-γ-butyrolactone or tulipaline A (1) and γ-butyrolactone (3) were active against M. incognita with an EC50/48h of 19.3±10.0 and 40.0±16.2mg/L respectively. Moreover the α, β-unsaturated lactone 5,6-dihydro-2H-pyran-2-one (2) exhibited the strongest nematicidal activity against the two species with EC50/48h 14.5±5.3 and 21.2±9.7mg/L respectively. Here we propose that the toxic effects of lactones and aldehydes on M.incognita and M. arenaria might be a consequence of their vacuolar-type H(+)-ATPase (V-ATPase) inhibition activity; in fact α-methylene-γ-butyrolactone (1) and salicylaldehyde (12) produced an increased pH in lysosomal-like organelles on HeLa human cell line and this alteration was most likely related to a V-ATPase impairment.

Keywords: Carbonyl compounds; HeLa cells; M. arenaria; M. incognita; Vacuolar-type H(+)-ATPase; α-Methylene-γ-butyrolactone.

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / chemistry
  • 4-Butyrolactone / pharmacology
  • Aldehydes / chemistry
  • Aldehydes / pharmacology
  • Animals
  • Antinematodal Agents / chemistry
  • Antinematodal Agents / pharmacology*
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • HeLa Cells
  • Helminth Proteins / antagonists & inhibitors*
  • Helminth Proteins / metabolism
  • Humans
  • Hydrogen-Ion Concentration / drug effects
  • Lactones / chemistry
  • Lactones / pharmacology
  • Lysosomes / drug effects
  • Lysosomes / metabolism
  • Microscopy, Fluorescence
  • Molecular Structure
  • Organelles / drug effects
  • Organelles / metabolism
  • Species Specificity
  • Structure-Activity Relationship
  • Tylenchoidea / classification
  • Tylenchoidea / drug effects
  • Tylenchoidea / enzymology
  • Vacuolar Proton-Translocating ATPases / antagonists & inhibitors*
  • Vacuolar Proton-Translocating ATPases / metabolism

Substances

  • Aldehydes
  • Antinematodal Agents
  • Helminth Proteins
  • Lactones
  • alpha-methylene gamma-butyrolactone
  • Vacuolar Proton-Translocating ATPases
  • 4-Butyrolactone