千年健萜类化学成分及其细胞毒活性研究

Terpenoids from rhizomes of Homalomena occulta and their cytotoxic activities

目的研究千年健Homalomenaocculta根茎的萜类化学成分及其细胞毒活性。方法应用硅胶柱色谱、Sephadex LH-20柱色谱、半制备型反相高效液相色谱和制备型薄层色谱等方法进行分离和纯化,通过MS、1D和2DNMR等波谱数据以及单晶X-射线衍射鉴定化合物的结构,采用MTT法测试化合物对3株人肝癌Hep G2、SMMC-7721和QGY-7703细胞的细胞毒活性。结果从千年健干燥根茎乙醇提取物的醋酸乙酯萃取部位得到11个萜类化合物,包括2个单萜:千年健烯A(1)、3,7-二甲基-1-辛烯-3,6-二醇(2);9个倍半萜:4(15)-eudesmene-1β,6α-diol(3)、菠萝香藤素(4)、1β,4α-dihydroxy-11,12,13-trinor-8,9-eudesmen-7-one(5)、1β,4β,7α-trihydroxyeudesmane(6)、mucrolidin(7)、bullatantriol(8)、cadinane-4β,5α,10α-triol(9)、4α-hydroxy-homalomenolC(10)、(1R,4S,5S,6S,7S,10R)-isodauc-6,7,10-triol(11)。结论化合物1为新化合物,化合物2为新天然产物,化合物3~5为首次从该属植物中分离得到,化合物10为首次从该植物分离得到,并首次报道化合物11的单晶结构。化合物5~7和9~11显示出细胞毒活性,化合物10的活性最好,对3种肿瘤细胞的半数抑制浓度(IC50)值分别为(37.56±6.73)、(33.39±2.75)和(44.24±5.15)μmol/L。

Objective To investigate the terpenoids from the rhizomes of Homalomena occulta and their cytotoxic activities.Methods The constituents were isolated and purified by using a combination of chromatographic techniques including column chromatography over silica gel and Sephadex LH-20,reverse-phase HPLC,and preparative thin layer chromatography.The structures were identified by analysis of the spectroscopic data and single crystal X-ray diffraction.The cytotoxic activities of the obtained compounds against human cancer cell lines Hep G2,SMMC-7721,and QGY-7703 were evaluated by MTT method.Results Eleven terpenoids were isolated from the Et OAc partition of the ethanolic extract of the rhizomes of H.occulta,including two monoterpenoids:homalomene A(1),and 3,7-dimethyl-1-octene-3,6-tetraol(2),and nine sesquiterpenoids:4(15)-eudesmene-1β,6α-diol(3),ananosmin(4),1β,4α-dihydroxy-11,12,13-trinor-8,9-eudesmen-7-one(5),1β,4β,7α-trihydroxyeudesmane(6),mucrolidin(7),bullatantriol(8),cadinane-4β,5α,10α-triol(9),4α-hydroxy-homalomenol C(10),and(1 R,4 S,5 S,6 S,7 S,10 R)-isodauc-6,7,10-triol(11).Conclusion Compound 1 is a new monoterpenoid,compound 2 is a new natural product,compounds 3—5 are isolated from the genus Homalomena for the first time,compound 10 is isolated from this plant for the first time,and the single-crystal structure of compound 11 is firstly reported.Compounds 5—7 and 9—11 show weak cytotoxic activities,and compound 10 exhibits the best inhibitory effects against the tested three human cancer cell lines with IC50 values of(37.56±6.73),(33.39±2.75),and(44.24±5.15)μmol/L,respectively.