Derivatives of schisandrin with increased inhibitory potential on prostaglandin E2 and leukotriene B4 formation in vitro |
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| Authors: | Martina Blunder Eva M Pferschy-Wenzig Walter MF Fabian Antje Hüfner Olaf Kunert Robert Saf Wolfgang Schühly Rudolf Bauer |
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| Institution: | 1. Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitaetsplatz 4, 8010 Graz, Austria;2. Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria;3. Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Universitaetsplatz 1, 8010 Graz, Austria;4. Institute for Chemistry and Technology of Materials, Graz University of Technology, Stremayrgasse 16, 8010 Graz, Austria |
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| Abstract: | Four derivatives of schisandrin, a major dibenzoa,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 LTB4 production the IC50 values of aR-6,7-dihydro-6-(1′-hydroxyethyl)-3,9-dimethoxy-6-methyl-5H-dibenzoa,c]cycloheptene-1,2,10,11-tetraol (6) and aR-6-(1′-iodoethyl)-1,2,3,9,10,11-hexamethoxy-6-methyl-5H-dibenzoa,c]cycloheptene (8) were 4.2 ± 0.3 μM and 4.5 ± 0.2 μM, respectively. aR-6,7-Dihydro-6-(1′-hydroxyethyl)-6-methyl-5H-dibenzoa,c]cycloheptene-1,2,3,9,10,11-hexaol (5) revealed dual inhibition on COX-2 (IC50 32.1 ± 2.5 μM) and on LTB4 production (37.3 ± 5.5% inhibition at 50 μM). |
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