Derivatives of schisandrin with increased inhibitory potential on prostaglandin E(2) and leukotriene B(4) formation in vitro.

Article Details

Citation

Copy to clipboard

Blunder M, Pferschy-Wenzig EM, Fabian WM, Hufner A, Kunert O, Saf R, Schuhly W, Bauer R

Derivatives of schisandrin with increased inhibitory potential on prostaglandin E(2) and leukotriene B(4) formation in vitro.

Bioorg Med Chem. 2010 Apr 1;18(7):2809-15. doi: 10.1016/j.bmc.2009.10.031. Epub 2009 Oct 20.

PubMed ID

20236826 [ View in PubMed

]

Abstract

Four derivatives of schisandrin, a major dibenzo[a,c]cyclooctadiene lignan of Schisandra chinensis (Turcz.) Baillon were synthesized and structurally characterized by means of NMR and mass spectroscopy. Furthermore, axial chirality of the biphenyl system was determined by comparison of calculated with measured circular dichroism (CD) spectra. Three of the obtained derivatives showed a ring contraction during chemical modification. While the original lignans were inactive on the performed bioassays, the compounds which showed the cycloheptadiene skeleton revealed remarkable activities. For the inhibition of LTB(4) production the IC(50) values of aR-6,7-dihydro-6-(1'-hydroxyethyl)-3,9-dimethoxy-6-methyl-5H-dibenzo[a,c]cyclohep tene-1,2,10,11-tetraol (6) and aR-6-(1'-iodoethyl)-1,2,3,9,10,11-hexamethoxy-6-methyl-5H-dibenzo[a,c]cyclohepten e (8) were 4.2+/-0.3microM and 4.5+/-0.2microM, respectively. aR-6,7-Dihydro-6-(1'-hydroxyethyl)-6-methyl-5H-dibenzo[a,c]cycloheptene-1,2,3,9,1 0,11-hexaol (5) revealed dual inhibition on COX-2 (IC(50) 32.1+/-2.5microM) and on LTB(4) production (37.3+/-5.5% inhibition at 50microM).

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Zileuton	Arachidonate 5-lipoxygenase	IC 50 (nM)	5000	N/A	N/A	Details