Synthesis of phospholipase A2 inhibitory biflavonoids

A series of C–C biflavones was designed to investigate the relationship between structural array of different flavone–flavone subunit linkage and the inhibitory activity against phospholipase A2 (PLA2). Among six classes of C–C biflavones designed, four classes of C–C biflavones, which have flavone–flavone subunit linkages at A ring–A ring, A ring–B ring, B ring–B ring, and B ring–C ring, were synthesized. The synthetic biflavones exhibited somewhat different inhibitory activities against sPLA2-IIA. Among them, the biflavone a having a C–C 4′–4′ linkage showed comparable inhibitory activity with that of the natural biflavonoid, ochnaflavone, and 7-fold stronger activity than that of amentoflavone. Further chemical modification is being carried out in order to obtain the chemically optimized biflavonoids.