MOLECULAR DESIGN OF BIOACTIVE HYBRID COMPLEXES

生物活性杂化复合物的分子设计

• 批准号: 08404044
• 负责人: YANO Shigenobu
• 金额: $ 25.6万
• 依托单位: NARA WOMEN'S UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08404044/
• 关键词: BIOACTIVITY; INTERCALETER; HYBRID COMPLEX; GLYCOSIDE COMPLEX; ANTIFUNGAL ACTIVITY; PHOTOTOXITY; ANTITUMOR ACTIVITY; PORPHYRIN; 糖; 錯体化学; 白金錯体; ジアジド; 抗がん活性; 抗癌性; シスプラチン; ニッケル錯体; 配糖ジアミン; ハイブリッド; 抗ガン活性; 結晶解析

[Ni(aldose3-tren)]ィイD12+ィエD1(aldoseィイD23ィエD2-tren = tris(N-aldosyl-2-aminoethyl)amine) were successfully isolated and characterized including x-ray crystallography. Antitumor cis-dichloroplatinum(II) complexes linked to an intercalator via one methylene chain were prepared and characterized, and their intercalation with DNA was examined. Trimanganese complexes with a linear MnィイD1IIィエD1MnィイD1IIIィエD1MnィイD1IIィエD1assemblage bridged by carbohydrates were prepared and their magnetic properties were analyzed. Peroxo-bridged dinuclear cobalt(III) complex containing N-glycoside ligands from tris(2-aminoethyl)amine and D-Glucose were prepared and its reversible dioxygen binding property has been observed. Unprecedented chiral Inversion around the seven-coordinated cobalt center induced by an Interaction between sugars and sulfate anions has been discovered. Antifungal nickel(II) complexes derived from amino sugars against pathogenic yeast, Candida Albicans were newly developed. First zinc(II) complexes containing N-glycosides derived from ethylenediamine and D-glucosamine were prepared and characterized. General Synthetic method of useful chelating reagents having a sugar unit via o-glycoside linkage was developed and effective antitumor cisplatin type complexes were developed. Sugar-dependent photocytotoxic property of tetra- and octa-glycoconjugated tetraphenylporphyrins has been examined. Effective phototoxic property of newly prepared tetra- and octa-glycoconjugated tetraphenylchlorins was observed.

[Ni（aldose 3-tren）]三（N-氨基乙基）胺D12+三（N-氨基乙基）胺D1（醛糖三（N-醛基）胺D23）被成功地分离和表征，包括X-射线晶体学。抗肿瘤顺式二氯铂（II）配合物连接到嵌入剂通过一个亚甲基链的制备和表征，并检查其嵌入与DNA。合成了由碳水化合物桥联的线型Mn D1 Ⅱ D1 Mn D1 Ⅲ D1 Mn D1 Ⅱ D1系列的三锰配合物，并对其磁性进行了分析。以三（2-氨基乙基）胺和D-葡萄糖为配体，合成了过氧桥联双核钴（III）配合物，并观察了其可逆的氧键合性质。发现了由糖与硫酸根阴离子的相互作用引起的围绕七配位钴中心的前所未有的手性反转。本文报道了一种新的氨基糖镍配合物对致病酵母白假丝酵母的抗真菌作用。首先，制备并表征了含有来自乙二胺和D-葡糖胺的N-糖苷的锌（II）络合物。开发了通过O-糖苷键具有糖单元的有用螯合剂的合成方法，并开发了有效的抗肿瘤顺铂型络合物。研究了四-和八-糖基共轭四苯基卟啉的糖依赖性光细胞毒性。观察到新合成的四-和八-糖基共轭四苯基二氢卟啉的有效光毒性。

项目成果

Y.Mikata, M.Yokoyama, S.Ogura, I.Okura, M.Kawasaki, M.Maeda and S.Yano: "Effect of side chain location in (2-aminoethyl)aminomethyl-2-phenylquinolins as antitumor agents"Bioorg. Med. Chem. Lett.. 8. 1243-1248 (1998)

Y.Mikata、M.Yokoyama、S.Ogura、I.Okura、M.Kawasaki、M.Maeda 和 S.Yano：“（2-氨基乙基）氨基甲基-2-苯基喹啉中侧链位置作为抗肿瘤剂的影响”Bioorg

Y. Mikata: "Synthesis, Characterization, Intercalation with DNA, and Antitumor Activity of a cis-Dichloroplatinum (II) Complex Linked to an Intercalator via one Methylene Chain"Bioorg. Med. Chem. Lett.. 7 (8). 1083-1086 (1997)

Y. Mikata：“通过一条亚甲基链与嵌入剂连接的顺式二氯铂 (II) 复合物的合成、表征、DNA 嵌入和抗肿瘤活性”Bioorg。

Y. Mikata: "Effect of side chain location in (20aminoethyl)aminomethyl-2-phenylquinolins as antitumor agents"Bioorg. Med. Chem. Lett.. 8. 1243-1248 (1998)

Y. Mikata：“（20氨基乙基）氨基甲基-2-苯基喹啉作为抗肿瘤剂侧链位置的影响”Bioorg。

S.Yano, M.Doi, S.Tamakoshi, W.Mori, M.Mikuriya, A.Ichimura, I.Kinoshita, Y.Yamamoto and T.Tanase: "Trimanganese complexes with a linear MnIIMnIIIMnII assemblage bridged by carbohydarates"Chem. Commun.. 997-998 (1997)

S.Yano、M.Doi、S.Tamakoshi、W.Mori、M.Mikuriya、A.Ichimura、I.Kinoshita、Y.Yamamoto 和 T.Tanase：“具有由碳水化合物桥接的线性 MnIIMnIIIMnII 组合的三锰配合物”Chem。

T. Tanase: "Assembly of Carbohydrates on Nickel (II) Center by Utilizing N-Glycosidic Bond Formation with Tris(2-aminoethyl)amine(tren). Syntheses and Characterization of [Ni{N-(aldosl)-tren}(H_2O)]^<2+>, [Ni{N,N'-di(aldoxyl)-tren}]^<2+> and [Ni{N,N',N''-

T. Tanase：“利用三(2-氨基乙基)胺(tren)形成N-糖苷键在镍(II)中心组装碳水化合物。[Ni{N-(aldosl)-tren}(H_2O)的合成和表征”