Development of bioprobes which regulate mammalian cell cycle

开发调节哺乳动物细胞周期的生物探针

• 批准号: 07660128
• 负责人: OSADA Hiroyuki
• 金额: $ 1.41万
• 依托单位: The Institte of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07660128/
• 关键词: cell cycle; taxol; cdc 2 kinase; inhibitor; tryprostration; acetophthalidin; 低分子プローブ; 真核細胞; 微生物産物

Cancer cells are uncontrolled cells with deregulation of the cell cycle, therefore, new cell cycle inhibitors might be good candidates for caner chemotherapy and also be a source for providing moleclar probes useful in elucidating regulatory mechanism of the cell cycle.We have begun on the screening for new cell cycle inhibitors from microbial origin. During the screening, we have isolated novel diketopiperazine alkaloids, spirotryprostatins A,B,tryprostatins A,B and cyclotryprostatins B,D,together with three new natural diketopiperazines, cyclotryprostatins A,C and demethoxyfumitremorgin C,as well as several known diketopiperazines such as fumitremorgin C from the fermetation broth of a fungus, Aspergillus fumigatus BM939, through a separation procedure guided by inhibitory activity on the cell cycle progression of mouse tsFT210 cells. Compoiunds inhibited the cell cycle progression of tsFT210 cells at G2 or phase in the dose range of micromolar order.Strctures of the new natural products obtained were determined mainly by the use of spectroscopic methods especially by detailed analyzes of their ^1H and ^<13>C NMR spectra with the aid of 2D NMR spectroscopy.

肿瘤细胞是一种细胞周期失控的细胞，因此，新的细胞周期抑制剂可能是肿瘤化疗的良好候选药物，也是阐明细胞周期调控机制的分子探针的来源。在筛选过程中，我们已经从真菌烟曲霉BM 939的发酵液中分离出新的二酮哌嗪生物碱，螺旋前列腺素A、B，前列腺素A、B和环前列腺素B、D，以及三种新的天然二酮哌嗪，环前列腺素A、C和去甲氧基烟曲霉素C，以及几种已知的二酮哌嗪如烟曲霉素C，通过对小鼠tsFT 210细胞的细胞周期进程的抑制活性指导的分离程序。化合物在微摩尔量级的剂量范围内可抑制tsFT 210细胞的G2期或G3期细胞的生长，其结构主要通过波谱学方法，特别是通过2DNMR对化合物的^1H和13CNMR谱进行了详细的分析<13>。

项目成果

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Matsuura,N.,et al：“磷胺苷和磷胺苷 B（一种新分离的衍生物）对 src 转化的 NRK 细胞的形态逆转活性。”

Nishiyama, U., M.Ubukata, J.Magae, T.Kataoka, F.Erdodi, J.H.D,K.Isono, K.Nagai & H.Osada: "Structureactivity relationship within a series of degradation products of tautomycin" Biosci. Biotech. Biochem. 60. 103-107 (1996)

西山，U.，M.Ubukata，J.Magae，T.Kataoka，F.Erdodi，J.H.D，K.Isono，K.Nagai

長田裕之(分担): "分子腫瘍学「細胞周期と細胞内シグナル伝達の阻害剤の項目」" 中外医学社:佐藤昇志、菊地浩吉編, 401-413 (1996)

Hiroyuki Nagata（撰稿人）：“分子肿瘤学‘细胞周期和细胞内信号转导的抑制剂’”Chugai Igakusha：Shoshi Sato、Kokichi Kikuchi，eds.，401-413（1996）

Hamaguchi, T., et al: "RK-682, a potent inhibitor of tyrosine phosphatase, arrested the mammalian cell cycle progression at G1 phase." FEBS Lett.372. 54-58 (1995)

Hamaguchi, T. 等人：“RK-682 是一种有效的酪氨酸磷酸酶抑制剂，可将哺乳动物细胞周期进程阻止在 G1 期。”

Nishiyama,U.,et al: "Structure activity relationship within a series of degradation products of tautomycin." Biosci.Biotech.Biochem.60. 103-107 (1996)

Nishiyama, U., et al：“互变霉素一系列降解产物内的结构活性关系。”