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

钩吻生物碱的研究，用于发现和开发新的抗肿瘤天然产物。

• 批准号: 16510156
• 负责人: KITAJIMA Mariko
• 金额: $ 2.5万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16510156/
• 关键词: Loganiaceae; Gelsemium elegans; Gelsemium sempervirens; alkaloid; gelsedine; cytotoxicity; EC_<50>; antitumor activity; イロドイド; 化学変換; イリドイド; マナン科; 細胞毒性; 2-アシルインドール

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)].

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)]。

项目成果

Isolation, Structure Elucidation, and Total Synthesis of Two New Chimonanthus Alkaloids, Chimonamidine and Chimonanthidine.

• DOI: 10.1002/chin.200423216
• 发表时间: 2004-01
• 期刊: ChemInform
• 作者: H. Takayama;Yohei Matsuda;K. Masubuchi;Atsushi Ishida;M. Kitajima;N. Aimi

Four novel gelsenicine-related oxindole alkaloids from the leaves of Gelsemium elegans Benth.

• DOI: 10.1021/ol061062i
• 发表时间: 2006-07-06
• 期刊: ORGANIC LETTERS
• 影响因子: 5.2
• 作者: Kogure, Noriyuki;Ishii, Naoko;Takayama, Hiromitsu
• 通讯作者: Takayama, Hiromitsu

New Oleanan-Type Triterpene and Cincholic Acid Glycosides from Peruvian “Una de Gato” (Uncaria tomentosa).

来自秘鲁“Una de Gato”（Uncaria tomentosa）的新齐墩果聚糖型三萜和钦胆酸苷。

• DOI: 10.1002/chin.200517191
• 发表时间: 2005
• 作者: M. Kitajima;K. Hashimoto;M. Sandoval;N. Aimi;H. Takayama
• 通讯作者: H. Takayama

Isolation of gelsedine-type indole alkaloids from Gelsemium elegans and evaluation of the cytotoxic activity of Gelsemium alkaloids for A431 epidermoid carcinoma cells

• DOI: 10.1021/np060016o
• 发表时间: 2006-04-01
• 期刊: JOURNAL OF NATURAL PRODUCTS
• 影响因子: 5.1
• 作者: Kitajima, M;Nakamura, T;Takayama, H
• 通讯作者: Takayama, H

Total Synthesis and NMR Assignment of Ourouparine, a Yohimbane-type Indole Alkaloid Isolated from Gelsemium sempervirens.

乌鲁肝素（一种从永生钩吻中分离出来的育亨班型吲哚生物碱）的全合成和 NMR 归属。

• 发表时间: 2007
• 期刊: J.Nat.Med. 61・2
• 作者: N.Kogure;et al.
• 通讯作者: et al.