Search for new antitumor lead-compounds originated from plant alkaloids

寻找源自植物生物碱的新型抗肿瘤先导化合物

• 批准号: 22510224
• 负责人: KITAJIMA Mariko
• 金额: $ 2.83万
• 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: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22510224/
• 关键词: 天然物化学; 生物活性物質; アルカロイド; インドール; コルヒチン; 誘導体合成; プロドラッグ; 構造活性相関; 細胞毒性; 構造解析

To discover and develop lead-compounds for new antitumor medicines originated from plant alkaloids, chemical investigation and biological evaluation of Gelsemium alkaloids and colchicinoids were carried out. As results, several novel alkaloids were isolated from Gelsemium plants. Key intermediates of sarpagine-type alkaloids, one of the members of Gelsemium alkaloids, were synthesized utilizing gold-catalyzed cyclization. 4-Halocolchicines and 4-chlorocolchicine derivatives bearing anα-hydroxyacetoamide side chain at C-7 were found to show potent antitumor activities. Pro-drugs of highly-active colchicine derivatives were prepared and their selective toxicity to the tumor cells was evaluated.

为发现和开发植物生物碱类抗肿瘤新药的先导化合物，对钩吻生物碱和秋水仙碱进行了化学研究和生物活性评价。结果从钩吻属植物中分离得到几个新的生物碱。利用金催化的环化反应合成了钩吻生物碱中的沙巴碱型生物碱的关键中间体。在C-7位带有α-羟基乙酰胺侧链的4-卤代秋水仙碱和4-氯秋水仙碱衍生物显示出较强的抗肿瘤活性。制备了高活性秋水仙碱类前药，并评价了其对肿瘤细胞的选择性毒性。

项目成果

Colchicine誘導体を基盤としたプロドラッグ化合物の創製研究

基于秋水仙碱衍生物的前药化合物的制备研究

• 发表时间: 2011
• 作者: 山田洋介;他;北島満里子;北島満里子;八十歩直子,北島満里子,小暮紀行,高山廣光
• 通讯作者: 八十歩直子,北島満里子,小暮紀行,高山廣光

アカネ科Ophiorrhiza trichocarpon含有新規インドールアルカロイド配糖体の構造解析

毛果、蛇根、茜草科新型吲哚生物碱苷的结构分析

• 发表时间: 2011
• 作者: N.Yasobu;et al.;北島満里子,尾原聡子,小暮紀行,Dammrong Santiarworn,高山廣光
• 通讯作者: 北島満里子,尾原聡子,小暮紀行,Dammrong Santiarworn,高山廣光

Synthesis and Biological Evaluation of 4-Chlorocolchicine Derivatives as Potent Anticancer Agents with Broad Effective Dosage Ranges

4-氯秋水仙碱衍生物作为有效剂量范围广泛的强效抗癌剂的合成和生物学评价

• DOI: 10.1039/c2md20250f
• 发表时间: 2012
• 期刊: Med. Chem. Comm
• 作者: H. Nishiyama;M. Ono;T. Sugimoto;T.Sasai;N. Asakawa;T. Matsumoto;T. Yaegashi;M. Nagaoka;T. Matsuzaki;N. Kogure;M. Kitajima;and H. Takayama
• 通讯作者: and H. Takayama

Asymmetric Total Synthesis of an Iboga-Type Indole Alkaloid, Voacangalactone, Newly Isolated from Voacanga africana

• DOI: 10.1021/ol3027945
• 发表时间: 2012-11-16
• 期刊: ORGANIC LETTERS
• 影响因子: 5.2
• 作者: Harada, Masaya;Asaba, Ken Nunettsu;Takayama, Hiromitsu
• 通讯作者: Takayama, Hiromitsu

Metacolchicine, A New Colchicinoid from Sandersonia aurantiaca

Metacolchicine，一种来自Sandersonia aurantiaca的新秋水仙碱类化合物

• 发表时间: 2011
• 期刊: Heterocycles
• 影响因子: 0.6
• 作者: M. Kitajima;A. Tanaka;N. Kogure;and H. Takayama
• 通讯作者: and H. Takayama