Geranylated flavonoids from the roots of campylotropis hirtella and their immunosuppressive activities

In an effort to identify new immunosuppressive agents from natural sources, 12 new geranylated flavonoids, 5,7,4′-trihydroxy-3′-[7-hydroxy-3,7- dimethyl-2(E)-octenyl]isoflavone (1), a racemate of 5,7,2′,4′- tetrahydroxy-3′-[7-hydroxy-3,7-dimethyl-2(E)-octenyl]isoflavanone (2), 2″(S)-5,7-dihydroxy[2″-methyl-2″-(4-methyl-3-pentenyl)pyrano] -5″,6″:3′,4′-isoflavone (3), (2″S,3″R, 4″S)-5,7,3″,4″-tetrahydroxy[2″-methyl-2″-(4- methyl-3-pentenyl)pyrano]-5″,6″:3′,4′-isoflavone (4), a racemate of 3′-geranyl5,7,2′,4′-tetrahydroxyisoflavanone (5), a racemate of 3′-geranyl-4′-methoxy-5,7,2′- trihydroxyisoflavanone (6), 3′-geranyl-5,7,4′,5′- tetrahydroxyisoflavone (8), 3′-geranyl-5,7,2′,5′- tetrahydroxyisoflavone (9), 3′-geranyl-4′-methoxy-5,7,2′- trihydroxyisoflavone (10), 2(R),3(R)-3′-geranyl-2,3-trans-5,7,4′- trihydroxyflavonol (12), (2R,3R)-6-methyl-3′-geranyl-2,3-trans-5,7, 4′-trihydroxyflavonol (13), and 5,7-dihydroxy4′-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 IC50 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′ position was necessary for the activity. As many of the compounds exhibited good immunosuppressive activities, they may be promising as novel immunosuppressive agents.