Studies on the Gelsemium Alkaloids for the Discovery and Development of New Antitumor Natural Products.

为了发现新的抗肿瘤天然产物，我们对钩吻属植物中的生物碱进行了化学研究，并对钩吻生物碱对某些肿瘤细胞的细胞毒作用进行了评价。在对钩吻属植物化学成分进行详尽研究的基础上，从钩吻属植物中分离得到了8个新的甘尔尔丁类生物碱(甘尔地仑、14-乙氧基甘草胺、甘尔赛尼定、甘尔利酮、14-乙酰氧基-15-羟基甘草碱、14-羟基-19-氧基甘草碱、14-乙酰氧基明胶糖苷)。羟乙基地拉姆和14-乙氧基羟基地拉姆是首次发现的18，19-NOR类单萜吲哚生物碱。盖尔赛尼定和盖尔赛酮分别在与明胶有关的单萜类吲哚生物碱上含有额外的呋喃残基或环烯醚衍生物单元。从欧洲钩吻中分离得到5个新的柳珊瑚碱类生物碱(GleSemperine-A，-B，-C，D，19Z-16-epi-voacarine)和1个新的育亨班碱类生物碱(Sempervilam)，并测定了14种钩吻生物碱对人鳞状上皮癌细胞A431和大鼠肝癌细胞H4-II-E-C3的细胞毒作用。在14种生物碱中，14，15-二羟基胶状碱[EC_&lt；50&gt；0.25μM(A431)]等5种甘尔丁型生物碱具有较强的细胞毒作用[阳性对照，顺铂，EC_&lt；50&gt；3.5μM(A431)]。

To discover new antitumor natural products, we carried out the chemical investigation of the alkaloids in Gelsemium plants (Loganiaceae), and the evaluation of the cytotoxic effects of Gelsemium alkaloids on some tumor cells.By exhaustive investigation of the constituents in Gelsemium plants, eight new gelsedine-type alkaloids (gelsedilam, 14-acetoxygelsedilam, gelsefuranidine, gelseiridone, 14-acetoxygelsenicine, 14-acetoxy-15-hydroxygelsenicine, 14-hydroxy-19-oxogelsenicine, 14-acetoxygelselegine) were isolated from G. elegans. Gelsedilam and 14-acetoxygelsedilam are the first examples of 18,19-nor-type monoterpenoid indole alkaloids. Gelsefuranidine and gelseiridone have, respectively, an additional furan residue or an iridoid unit on the gelsenicine-related monoterpenoid indole alkaloid. From G. sempervirens, five new sarpagine-type alkaloids (gelsempervine-A, -B, -C, and -D, 19Z-16-epi-voacarpine) and one new yohimbane-type alkaloid (sempervilam) were isolated.The cytotoxic effects on fourteen Gelsemium alkaloids against the human squamous epithelioma cell line A431and rat hepatoma cell line H4-II-E-C3 were evaluated. Among the fourteen alkaloids, five gelsedine-type alkaloids including 14,15-dihydroxygelsenicine [EC_<50> 0.25 μM (A431)] showed strong cytotoxic effects [positive control, cisplatin, EC_<50> 3.5 μM (A431)].