Study on the Alkaloid Production of Two Gelsemium Plants by Using their Callus Cultures and Chemical and Pharmacological Investigation of Gelsemium Alkaloids.

两种钩吻植物愈伤组织培养物生产生物碱的研究及钩吻生物碱的化学和药理研究。

• 批准号: 14571996
• 负责人: KITAJIMA Mariko
• 金额: $ 2.3万
• 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: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571996/
• 关键词: Loganiaceae; Gelsemium elegans; Gelsemium sempervirens; alkaloid; callus; phylogenelic analyses of DNA; toxicity; antitumor activity; Gelsemium sempervirens; イリドイド; テルペン; 急性毒性; 毛状根; アゼチジン環; 系統解析

Gelsemium elegant and G.sempervirens belonging to Loganiaceae are known to be toxic and rich sources of indole alkaloids.Callus cultures of Gelsemium plants were successfully obtained from the leaf segments of G.elegans and G.sempervirens, respectively. By the chemical investigation of G.sempervirens callus, it became clear that the callus did not produce alkaloidal constituents.Phylogenetic comparison of DNA among G.elegans, G.sempervirens, Strychnos nux-vomica and Gardneria nutans were investigated. The analysis revealed that the two.Gelsemium plants formed a cluster but they were not closely related.By exhaustive investigation of the, constituents in Gelsemium plants, fourteen alkaloids including four new compounds (14,15-dihydroxygelsenicine, GE-2, GE-3, GE-4) were isolated from the leaves of G.elegans. 14,15-Dihydroxygelsenicine is the first Gelsemium oxindole alkaloid having a vicinal diol. The stricture of the known alkaloid, gelsemoxonine, was revised to be a novel oxindole possessing an azetidine unit. This is the first example of the monoterpenoid indole alkaloid having an azetidine unit in the molecule. From the stems of G.sempervirens, fourteen compounds including three new oxindole alkaloids (GS-1, GS-2, GS-3) and one new iridoid (GSIR-1) were isolated. Among them, six compounds were also isolated from the leaves.Lethal effect of the representative Gelsemium alkaloids on rat hepatocytes (H4-II-E-C3 cell) was evaluated. It was found that koumine and humantenine were quite effective than antitumor reagent, cisplatin.

钩吻（Gelsemium elegans）和长山钩吻（G. sempervirens）是马钱科植物，有毒且富含吲哚类生物碱。通过化学成分分析，确定其不产生甾体类成分，并对秀丽隐杆线虫、地中海隐杆线虫、马钱子和垂枝栀子的DNA进行了系统发育分析。通过对钩吻属植物化学成分的研究，从钩吻属植物叶中分离得到14种生物碱，其中包括4个新化合物（14，15-dihydroxygelsenicine，GE-2，GE-3，GE-4）。14，15-Dihydroxygelsenicine是第一个含有邻位二醇的钩吻属羟吲哚生物碱。将已知生物碱gelsemoxidine的结构修改为具有氮杂环丁烷单元的新型羟吲哚。这是分子中具有氮杂环丁烷单元的单萜类吲哚生物碱的第一个例子。从地中海棉茎中分离得到14个化合物，其中包括3个新的氧化吲哚生物碱（GS-1，GS-2，GS-3）和1个新的环烯醚萜（GSIR-1）。从钩吻叶中分离得到6个化合物，并对其中的代表性化合物进行了大鼠肝细胞（H4-II-E-C3细胞）的致死作用研究。结果表明，钩吻素和乌曼地宁的抗肿瘤作用优于顺铂。

项目成果

M.Kitajima et al.: "Camptothecin-related Alkaloids from Hairy Roots of Ophiorrhiza pumila."Tetrahedron. 58. 9169-9178 (2002)

M.Kitajima 等人：“来自蛇根毛根的喜树碱相关生物碱。”四面体。

M.Kitajima et al.: "Structure Reinvestigation of Gelsemoxonine, a Constituent of Gelsemium elegans, Reveals a Novel, Azetidine-Containing Indole Alkaloid."Org.Lett.. 5. 2075-2078 (2002)

M.Kitajima 等人：“钩吻素（一种秀丽隐杆线虫的成分）的结构重新研究，揭示了一种新颖的含氮杂环丁烷的吲哚生物碱。”Org.Lett.. 5. 2075-2078 (2002)

H.Takayama, et al.: "Seven New Lycoposium Alkaloids, Lycoposerramines, from Lycposium serratum Thunb"Tetrahedron Lett.. 43・46. 8307-8311 (2002)

H. Takayama 等人：“来自 serratum Thunb 的七种新的石松属生物碱，石松胺” Tetrahedron Lett.. 8307-8311 (2002)。

M.Kitajima et al.: "Camptothecin-related Alkaloids from Culture Medium of Hairy Roots of Ophiprrhiza pumila."Natural Medicines. 56(6). 275 (2002)

M.Kitajima 等人：“蛇后毛根培养基中的喜树碱相关生物碱。”天然药物。

M.Kitajima et al.: "Synthesis and Absolute Configuration of a New 3,4-Dihydro-β-carboline-Type Alkaloid,3,4-Dehydro-5(S)-5-carboxystrictosidine, Isolated from Peruvian Uta de Gato (Uncaria tomentosa)."Chem.Pharm.Bull.. 50(10). 1376-1378 (2002)

M.Kitajima 等人：“从秘鲁 Uta de Gato 中分离出的新型 3,4-二氢-β-咔啉型生物碱 3,4-脱氢-5(S)-5-羧基胡豆素的合成和绝对构型（毛钩藤).“Chem.Pharm.Bull..50(10).1376-1378(2002)