生体高分子機能を修飾する抗がん化合物の合成と作用解析

改变生物聚合物功能的抗癌化合物的合成和作用分析

• 批准号: 07274101
• 负责人: 松田 彰
• 金额: $ 11.52万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-07274101/
• 关键词: 生体高分子; 代謝拮抗剤; ハリコンンドリンB; タキリ-ル; レチノイド; ネオカルチノスタチン; サイクリックADPリボース; アポトーシス

本年度の研究で以下のことを明らかにした.がん細胞のDNA,RNA合成の両者を阻害するヌクレオシドとして設計した3′-C-ethynyluridine(EUrd)および-cytidine(ECyd)はin vitroのみならずin vivoでも優れた抗がん性を示した.抗がん剤ネオカルチノスタチンの光分解経路の解明に成功し、新しい光缶応型のDNA切断分子を設計した.日本産イチイ葉から得られるタキシニンの化学修飾により分化誘導作用を示す化合物を得た.優れた抗がん性を示すハリコンドリンBの全合成にあと一歩のところまで近づいた.細胞分化の特異的調節因子であるレチノイン酸の作用を制御する化合物として、その拮抗物質、作用増強物質を合成した.サイクリックADPリボース安定等価体と考えられるカーボサイクリックIDPリボースを合成した.固形がんに有効な新規deoxycytidine誘導体KW-2331はがん細胞内で代謝活性化され、cytidine deaminaseにより不活性化されないことを明らかにした.ヒト腫瘍HT1080細胞のCNDAC耐性株はcytidine deaminase活性が親株より強く、deoxycytidine Kinase活性が低下していることを見い出した.アポトーシスを起こす細胞内のpHが酸性になり、新しいendonucleaseが活性化されDNA二本鎖を起こすことが判った.新規抗がん性ヌクレオシドCNDAC,DMDCの作用機序研究により、それらの抗がん性の発現にDNA修復系の関与を示唆する知見を得た.

The following studies will be conducted this year. The DNA,RNA synthesizer is used to prevent the damage from the device. The device is 3'-C-ethynyluridine (EUrd) integrated-cytidine (ECyd). The in vitro generator is sensitive to in vivo. The anti-jamming performance is displayed. The photolysis circuit was successfully resolved, and the new photoluminescence DNA cut-off molecular device was designed. In Japan, the chemical reaction was obtained by chemical modification. The differentiation effect showed that the compounds were isolated. The resistance shows that it is not easy to make a full synthesis of the whole body. The specific factors of cell differentiation, such as the action of acid to control the synthesis of compounds, antagonists, potent agents and synthetic agents. I don't know what to say about ADP, diazepam and so on. I don't know. I don't know. There are some new deoxycytidine drugs, such as KW-2331, intracellular activation, cytidine deaminase inactivation, inactivation, and so on. The CNDAC-tolerant plants showed strong cytidine deaminase activity and low deoxycytidine Kinase activity, while the CNDAC-tolerant plants showed strong cytidine deaminase activity and low deoxycytidine Kinase activity. In the first place, the intracellular pH acidosis, the activation of endonuclease, the activation of DNA in ordinary universities, and the diagnosis of DNA were detected. A study on the mechanism of the action of anti-inflammatory drugs in the new regulations; the effect of anti-inflammatory drugs on CNDAC,DMDC has shown that the DNA system has been modified and instigated to obtain information.

项目成果

Kiyoshi Horita: "Stereoselectiue total synttresis of Cysocellin, the representatiue polyettrer antibiotic of the lysocellin fanuly." Tetrahedron. 52. 551-564 (1996)

Kiyoshi Horita：“立体选择性全合成溶细胞素，溶细胞素的代表性多聚抗生素。”

Atsushi Azuma: "Chemical stability of new antilumor nucleoside, 2′-C-cyano-2′-deoxy-1-B-D-arabino-peutofuranosylcytosine" J. Med. Chem.38. 3391-3397 (1995)

Atsushi Azuma：“新型抗肿瘤核苷 2′-C-cyano-2′-deoxy-1-B-D-arabino-peutofuranosylcytosine 的化学稳定性”J. Med. 3391-3397 (1995)。

Satoshi Shuto: "Antitumor Phospholipids with 5-fluoerouidine as a cytotoxic ptolan head Synthesis of 5'-phosphatidyl-5-fluorowidines" Bioorganis K Medicinal Chem. 3. 235-243 (1995)

Satoshi Shuto：“以 5-氟代环苷作为细胞毒性 ptolan 头的抗肿瘤磷脂，5-磷脂酰-5-氟代环苷的合成”Bioorganis K 医药化学。

Akihiro Tomida: "Acute induction of adriamycin-resistance in human colon carcinoma HT-29cells exposed to a sublethal dose" Jpn. J. Cancer Res. 86. 224-232 (1995)

Akihiro Tomida：“暴露于亚致死剂量的人结肠癌 HT-29 细胞中急性诱导阿霉素耐药性”Jpn。

Motohiro Tanaka: "Photodynamic therapy of photofrinII and excimer dye laser on experimemtal tumors" Cancer Lett,.90. 163-169 (1995)

Motohiro Tanaka：“photofrinII 和准分子染料激光对实验肿瘤的光动力疗法”Cancer Lett，.90。