Study On Structural Modifications And Anticancer Activity Of Cantharidin And Its Derivatives

Cantharidin is monomer compound extracted from the body of a kind of Meloidae insects-cantharis.The chemical structure of cantharidin is C10H12O4,The chemical name is exo-1,2-cis-dimethy 1-3,6-epoxyhexahydrophthalic anhydride,and it belongs to half terpene derivatives.Cantharidin has good curative effect to a variety of cancer,But as a result of severe irritation to urinary system and intense excitant toxicity,its clinical has been limited greatly.At present,although a variety of cantharidin derivatives,such as norcantharidin and Cantharidin acid sodium,has a good curative effect on many cancers including primary liver cancer,the appearance of a variety of adverse reactions when using such compounds in expanding dose is still the reason of restricting their play a greater role in clinic use.In this paper,on the basis of predecessors' research,the double bond,anhydride ring and oxygen bridge on the structure of cantharidin are modified and transformed.Seven compounds are obtained.They are:7-oxygen mixed double loop[2.2.1]heptane-5-ene-2,3-dimethyl anhydride;7-oxygen impurity bicyclic[2.2.1]-2,3-dimethyl anhydride;3,8 oxygen impurity three-ring[3.2.1.024]octane-6,7-2 formic acid;3,8 oxygen impurity three-ring[3.2.1.0 24]octane-6,7-dimethyl anhydride;N-ethyl-7 oxygen mixed double loop[2.2.1]heptane-5-ene-2,3-2 formyl imine;5,6-dibromo-oxygen impurity bicyclic[2.2.1]octane-2,3-dimethyl anhydride and victor anhydride.Their structures are confirmed by NMR.The influence of seven compounds on proliferation of three types of human cancer cellsHepG2?A549?MCF-7 is researched by MTT.The structure-activity relationship between cantharis anticancer activities in vitro and modification and retrofit in in different functional group on the structure of cantharidin is inspected.The results show that:In addition to the victor anhydride,all the other six compounds have certain inhibitory activity on three kind of human cancer cells.Excitant toxicity of six compounds which have good anticancer activity are investigated by rabbit eye stimulation method.The results show that:Compared with other compounds,7-oxygen mixed double loop[2.2.1]heptane-5-ene-2,3-dimethyl anhydride and N-ethyl-7 oxygen mixed double loop[2.2.1]heptane-5-ene-2,3-2 formyl imine have strong excitant toxicity.