Synthesis of Antitumor Antibiotics and their Model Compounds

抗肿瘤抗生素及其模型化合物的合成

• 批准号: 62570941
• 负责人: SHIBUYA Masayuki
• 金额: $ 1.09万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570941/
• 关键词: Carzinophilin; Azinomycin; Neocarzinostatin; Antibiotic; Chemical Structure; Chemical Synthesis; DNAの切断; 紫外線; 抗腫瘍活性; NDAの切断; 絶対配置

Carzinophilin (CZ) and Neocarzinostatin Chromophore (NCS-Chr) are well known antitumor antibiotics, the structures of which are still not established. We predicted that cz is the same compound as Azinomycin which has been isolated by the research group of SS-Pharm, Co., and confirmed that by the synthesis of its left moiety. For the total synthesis of CZ (Azinomycin), we established the effective synthetic methods. In relation to the in vivo antitumor mechanisms of NCS-Chr, we synthesized oligo-N-methyl pyrrole derivatives by use of novel and efficient method. The DNA-cleaving activity of synthetic compounds under photo irradiation was investigated. Other heterocyclic compounds such as AK-toxin and some thiadiazoles were synthesized in order to search effective antitumor compounds. The test of bioactivities of synthetic compounds is under progress.

Carzinophilin (CZ) 和 Neocarzinostatin Chromophore (NCS-Chr) 是众所周知的抗肿瘤抗生素，但其结构尚未确定。我们预测cz与SS-Pharm公司研究小组分离出的Azinomycin是同一化合物，并通过其左侧部分的合成证实了这一点。对于CZ（阿嗪霉素）的全合成，我们建立了有效的合成方法。针对NCS-Chr的体内抗肿瘤机制，我们采用新颖高效的方法合成了低聚-N-甲基吡咯衍生物。研究了光照射下合成化合物的 DNA 切割活性。为了寻找有效的抗肿瘤化合物，还合成了AK-毒素和一些噻二唑等其他杂环化合物。合成化合物的生物活性测试正在进行中。

项目成果

Kouhei Toyooka: Chem.Pharm.Bull.35. 1030-1035 (1987)

Kouhei Toyooka：Chem.Pharm.Bull.35。

Kouhei Toyooka: Chem.Pharm.Bull.36. 96-106 (1988)

Kouhei Toyooka：Chem.Pharm.Bull.36。

Jun Kawada: "Protective Effect of 4,6-O-Ethylidene Glucose Against the Cytotoxicity of Streptozotocin in Pancreatic Cells in vivo" J. Endocr.112. 375-378 (1987)

Jun Kawada：“4,6-O-亚乙基葡萄糖对体内胰腺细胞中链脲佐菌素细胞毒性的保护作用”J. Endocr.112。

Masayuki Shibuya: Tetrahedron Letters. 28. 2619-2622 (1987)

涩谷雅之：四面体字母。

Yoshihisa Takaishi: Phytochemistry. 26. 2581-2584 (1987)

高石义久：植物化学。