Geranylated Flavonoids from the Roots of Campylotropis hirtella and Their Immunosuppressive Activities (original) (raw)

2009, Journal of Agricultural and Food Chemistry

In an effort to identify new immunosuppressive agents from natural sources, 12 new geranylated flavonoids, 5,7,4 0-trihydroxy-3 0-[7-hydroxy-3,7-dimethyl-2(E)-octenyl]isoflavone (1), a racemate of 5,7,2 0 ,4 0-tetrahydroxy-3 0-[7-hydroxy-3,7-dimethyl-2(E)-octenyl]isoflavanone (2), 2 00 (S)-5,7-dihydroxy-[2 00-methyl-2 00-(4-methyl-3-pentenyl)pyrano]-5 00 ,6 00 :3 0 ,4 0-isoflavone (3), (2 00 S,3 00 R,4 00 S)-5,7,3 00 ,4 00-tetrahydroxy[2 00-methyl-2 00-(4-methyl-3-pentenyl)pyrano]-5 00 ,6 00 :3 0 ,4 0-isoflavone (4), a racemate of 3 0-geranyl-5,7,2 0 ,4 0-tetrahydroxyisoflavanone (5), a racemate of 3 0-geranyl-4 0-methoxy-5,7,2 0-trihydroxyisoflavanone (6), 3 0-geranyl-5,7,4 0 ,5 0-tetrahydroxyisoflavone (8), 3 0-geranyl-5,7,2 0 ,5 0-tetrahydroxyisoflavone (9), 3 0-geranyl-4 0-methoxy-5,7,2 0-trihydroxyisoflavone (10), 2(R),3(R)-3 0-geranyl-2,3-trans-5,7,4 0-trihydroxyflavonol (12), (2R,3R)-6-methyl-3 0-geranyl-2,3-trans-5,7,4 0-trihydroxyflavonol (13), and 5,7-dihydroxy-4 0-O-geranylisoflavone (14), were isolated from the roots of Campylotropis hirtella (Franch.) Schindl. together with three previously described flavonoids. Their structures were elucidated by spectroscopic measurements, including two-dimensional nuclear magnetic resonance (NMR) techniques. The immunosuppressive effects of these compounds were assessed using mitogen-induced splenocyte proliferation, and the cytotoxicity of the compounds was also examined. The IC 50 values of the compounds were found to be in the range of 1.49-61.23 μM for T lymphocyte suppression and 1.16-73.07 μM for B lymphocyte suppression. An analysis of their structure-activity relationships revealed that an isoflavonoid carbon skeleton with a C10 substituent at the C3 0 position was necessary for the activity. As many of the compounds exhibited good immunosuppressive activities, they may be promising as novel immunosuppressive agents.