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

作者：Blunder Martina; Pferschy Wenzig Eva M; Fabian Walter M F; Huefner Antje; Kunert Olaf; Saf Robert; Schuehly Wolfgang; Bauer Rudolf^*

来源：Bioorganic & Medicinal Chemistry, 2010, 18(7): 2809-2815.

DOI：10.1016/j.bmc.2009.10.031

• Schisandra chinensis lignans
• Schisandrin
• Derivatives
• Demethylation
• Ring contraction
• Cyclooxygenase
• Lipoxygenase

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 LTB4 production the IC50 values of aR-6,7-dihydro-6-(1'-hydroxyethyl)-3,9-dimethoxy-6-methyl-5H-dibenzo[a,c]cycloheptene-1,2,10,11-tetraol (6) and aR-6-(1'-iodoethyl)-1,2,3,9,10,11-hexamethoxy-6-methyl-5H-dibenzo[a,c]cycloheptene (8) were 4.2 +/- 0.3 mu M and 4.5 +/- 0.2 mu M, respectively. aR-6,7-Dihydro-6-(10-hydroxyethyl)-6-methyl-5H-dibenzo[a,c]cycloheptene-1,2,3,9,10,11-hexaol (5) revealed dual inhibition on COX-2 (IC50 32.1 +/- 2.5 mu M) and on LTB4 production (37.3 +/- 5.5% inhibition at 50 mu M).

• 出版日期2010-4