Planta Med 2013; 79 - PI91
DOI: 10.1055/s-0033-1352180

Jatrophane diterpenoids with multidrug resistance-modulating activity from Euphorbia exigua

D Rédei 1, K Boros 1, P Forgo 1, G Pinke 2, J Molnár 3, J Hohmann 1
  • 1University of Szeged, Department of Pharmacognosy, Szeged, Hungary
  • 2University of West Hungary, Faculty of Agricultural and Food Sciences, Department of Botany, Mosonmagyaróvár, Hungary
  • 3University of Szeged, Department of Medical Microbiology and Immunobiology, Szeged, Hungary

A primary mechanism of resistance to multiple anticancer drugs is the overproduction of permeability glycoprotein (P gp) in plasma membranes of resistant cells. The P gp acts as an energy-dependent efflux pump, reducing the intracellular accumulation of drug molecules. In recent years, considerable attention has been devoted to the development of new effective multidrug resistance (MDR) modulating agents from natural sources. Promising group of anti-MDR molecules are the macrocyclic diterpenes from Euphorbiaceae species.

We report herein the isolation and structure determination of diterpenes from Euphorbia exigua L., an annual weed with Southern-temperate distribution, whose diterpene constituents has not been reported previously.

The methanol extract of the fresh aerial parts of E. exigua was subjected to solvent partitioning to furnish chloroform- and water-soluble fractions. The organic phase was fractionated by column chromatography on polyamide, then by vacuum liquid chromatography on silica gel. Selected fractions were further purified by CPC, preparative TLC and HPLC to yield three pure compounds. The structure elucidation was carried out by HRESIMS and extensive NMR studies using advanced experiments (1H NMR, JMOD, 1H-1H COSY, HSQC and HMBC).

The isolated compounds were identified as jatrophane polyesters. Two of them are new natural compounds acylated with acetic, benzoic, propanoic, angelic and cinnamic acids. One compound proved to be identical with isoterracinolide B isolated earlier only from Euphorbia terracina.

The investigation of the compounds for modulating intracellular drug accumulation of MDR mouse lymphoma cells resulted that all three compounds promoted the accumulation of rhodamine 123 at a level similar to the parental cell line which do not over-express the MDR1 pump.

This work was supported by European Union and co-funded by the European Social Fund (TÁMOP-4.2.2.A-11/1/KONV-2012 – 0035) and Hungarian Scientific Research Fund (OTKA) (PD 78145).