Development of practical supply of isoquinoline marine natural products to designate the creation of the new anticancer agents

开发异喹啉海洋天然产品的实际供应以指定新抗癌剂的创建

• 批准号: 16590019
• 负责人: SAITO Naoki
• 金额: $ 1.73万
• 依托单位: Meiji Pharmaceutical 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 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590019/
• 关键词: Marine Natural Product; Renieramycin; Jorunnamycin; Oxidative Degradation; Anticancer Agent; Structure Activity Relationship; Chemical Transformation; Isoquinoline Alkaloid; 創薬; 海洋資源; 天然物化学; アルカロイド; 海綿; ウミウシ; ジョルマイシン; 酸化的分解反応

As a part of our search for new anticancer metabolites in the isolation and characterization of biologically active compounds from the Thai marine animals, we have succeeded to find blue sponges, Xestospongia sp. growing around Sichang Island in the Gulf of Thailand. We report the isolation and structure elucidation of renieramycin M as a major products pretreated marine animals with potassium cyanide in methanolic buffer solution. This is the first example for supply a gram scale of renieramycin type products from marine sources. Renieramycin M, which has potent strong cytotoxicity against several kinds of tumor cells, was easily transformed to jorumycin and renieramycin J, independently. We discovered that the oxidative degradation of jorumycin and renieramycin E to generate simple isoquinoline alkaloids, such as mimosamycin, renierone, and renierol acetate. Furthermore, jorunnamycins A-C, three novel cytotoxic renieramycin type compounds, were isolated from the Thai nudibranch, Jorunna funebris that was pretreated with potassium cyanide, along five known compounds. The structures of them ware elucidated from spectral data along with chemical transformation. Thus, renieramycins will be going up one of fascinated lead for development of new anticancer drug near future.

作为我们在从泰国海洋动物中分离和表征生物活性化合物的过程中寻找新的抗癌代谢物的一部分，我们成功地发现了蓝色海绵Xestospongia sp.。本文报道了用氰化钾在甲醇缓冲溶液中预处理海洋动物的主要产物雷那霉素M的分离和结构鉴定。这是第一个从海洋来源供应克级雷尼霉素类产品的例子。雷尼霉素M对多种肿瘤细胞具有较强的细胞毒活性，易转化为约鲁霉素和雷尼霉素J。我们发现，氧化降解jorumycin和renieramycin E生成简单的异喹啉生物碱，如mimosamycin，renierone和renierol acetate。此外，从用氰化钾预处理的泰国裸鳃亚目动物Jorunna funebris中分离出了三种新的细胞毒性雷那霉素类化合物Jorunnamycins A-C，以及沿着的五种已知化合物。通过沿着化学转化，从光谱数据上确定了它们的结构。因此，雷尼霉素类药物将成为开发新型抗肿瘤药物的热点之一。

项目成果

Jorunnamycins A-C Novel Cytotoxic Renieramycin Type Bistetrahydroisoquinolines isolated from the Thai Nudibranch Jorunna funebris

Jorunnamycins A-C 从泰国裸鳃亚目 Jorunna funebris 中分离出的新型细胞毒性雷尼尔霉素型双四氢异喹啉

• 期刊: J. Nat. Prod. (in press)
• 作者: Ikeuchi;Y;Taguchi;Hanzawa;Y.;H.Takahashi;Sumiaki Kodama et al.;Korunvika Charupant et al.
• 通讯作者: Korunvika Charupant et al.

Chemistry of renieramycins.: Part 5.: Structure elucidation of renieramycin-type derivatives O, Q, R, and S from Thai marine sponge Xestospongia species pretreated with potassium cyanide

• DOI: 10.1021/np030534o
• 发表时间: 2004-06-01
• 期刊: JOURNAL OF NATURAL PRODUCTS
• 影响因子: 5.1
• 作者: Amnuoypol, S;Suwanborirux, K;Saito, N
• 通讯作者: Saito, N

Chemistry of Antitumor Isoquinoline Alkaloids. Unexpected Oxidation of Saframycin S to Generate Simple Isoquinoline Alkaloids, Mimocin and Mimosamycin

抗肿瘤异喹啉生物碱的化学。

• 发表时间: 2003
• 期刊: Heterocycles 61 (1)
• 作者: K.Suda;T.Kikkawa;S.Nakajima;T.Takanami;Y.M.A.Yamada;Naoki Saito et al.
• 通讯作者: Naoki Saito et al.

Chemistry of Antitumor Isoquinoline Alkaloids : Unexpected Oxidation of Saframycin S to Generate Simple Isoquinoline Alkaloids, Mimosamycin and Momocin

抗肿瘤异喹啉生物碱的化学：Saframycin S 意外氧化生成简单的异喹啉生物碱、含羞霉素和莫莫星

• 发表时间: 2003
• 期刊: Heterocycles 61(1)
• 作者: Saito;N.;Koizumi;Y.;Suwanborirux;K.;Kubo;A.
• 通讯作者: A.

Structure and chemical property of three new marine alkaloids from the nudibranch Jorunna funebris which lives through in the blue sponge

来自生活在蓝色海绵中的裸鳃类 Jorunna funebris 的三种新海洋生物碱的结构和化学性质

• 发表时间: 2005
• 期刊: Yakugaku Zasshi 125, Suppl.3
• 作者: Naoki Saito;et al.
• 通讯作者: et al.