Synthesis of 3- and 5-β-anhydroicaritine norcantharidin conjugates

Using molecular hybridisation to develop conjugates of natural antitumor drugs is one of the research hotspots in recent drug development. In this study, β-anhydroicaritine with anticancer activity was conjugated to norcantharidine selectively to develop new antitumor lead candidates. In the condition of EDCI/DMAP/DCM, the C-3 and C-5 hydroxyl groups of β-anhydroicaritine was coupled with norcantharidin monoacid ester respectively, and the inhibitory activity of the synthesised conjugates against HepG2, MCF-7 and L-02 cells were tested by CCK-8 method. Most of these conjugates showed a better activity against HepG2 and MCF-7 cell lines compared to parent compound icaritin, but weaker than another parent compound norcantharidin.