Studies On The Chemical Constituents Of Ganoderma Luteomarginatum And Their Cytotoxicity Against Human Cancer Cell Lines

The G.luteomarginatum materials is derived from the dried fruit body of G.luteomarginatum.More than 100 Ganoderma species in China,and they have a long history of being used as traditional Chinese medicine for the treatment and prevention of various diseases in China.Ganoderma genus fungi were regarded as the almighty medicines due to their beneficial effects,such as longevity,health care,replenishing qi and blood,tranquilizing the mind,invigorating the spleen and stomach,etc.Literatures reported the ethanol extraction of G.luteomarginatum has obvious anti-tumor effect.In order to further explored anti-tumor material,its EtOAc extracts was systematically phytochemical investigated.The compounds were separated and repeatedly purified by column chromatography over silica gel and Sephadex LH-20,MPLC,preparative TLC,and semi-preparative HPLC.A total of 29 compounds were isolated from the EtOAc extracts of the fruiting bodies of G.luteomarginatum,including 20 lanostane triterpenoids and 9 ergostane-type steroids.These triterpenoids were further identified as 10 new compounds?1*-7*,14*-16*?and 10 known analogues?8-13,17-20?.Compounds 1 and 2 were novel triterpenoids with an unusual 26-nor-lanosta carbon skeleton only reported by one paper.Compounds 3 was a derivative of ganoderic acid,and COOH-26 cyclizated with OH-23 forming a pentatomic lactone ring.Furthermore,the cytotoxicities of these chemical components for four human cancer cell lines?HGC-27,HeLa,A549,and SMMC-7721?were measured by MTT method.Compound 7 exhibited the highest cytotoxicity against HeLa and A549 cell lines,with IC₅₀values of 1.29 and 1.50?M,respectively.Compounds 2*,4*,5*,7*,10,11,16*,and 20 also exhibited significant cytotoxicities against HGC-27 cells(IC₅₀<10?M)?Afterscreeningthecytotoxicactivityofthesecompounds,the structure-cytotoxicity relationship were preliminarily explored.The results showed that the substituents of C-3 and C-26 sites have significant influence on the cytotoxicity of these compounds.Reduction of keto-3 group to OH-3 or OAc-3improved the cytotoxicity significantly and oxidation of OH-26 in lanostane triterpenoids would result in a significant loss of the cytotoxicity on the four cell lines.In addition,the research progress of triterpenoids of Ganoderma genus fungi in the last five years was reviewed in this paper.The new compounds isolated from Ganoderma species in the last five years and their pharmacological activities were summarized,which provided some reference for the further research of Ganoderma triterpenoids.