Anticancer metal complexes developed by adsorption to apatite as an indicator

以磷灰石为指示剂吸附开发的抗癌金属配合物

• 批准号: 17550055
• 负责人: ODANI Akira
• 金额: $ 1.09万
• 依托单位: NAGOYA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17550055/
• 关键词: platinum(II) complexes; anticancer drug; bone; hydroxyapatite; adsorption; phosphate containing compounds; cisplatin; oxaliplatin; メチレンジホスホン酸

Clinical anticancer Pt(II) complexes such as cisplatin, carboplatin, and oxaliplatin commonly consist of 2N and 2C1 or 2O (carboxylate) as donor atoms. These Cl and O groups called "Leaving Group (LG)" have been believed to be less important because anticancer Pt(II) drugs attack the DNA base after dissociation of LG from the Pt(II) coordination. Recently LG has been studied as a tool of drug delivery system (DDS). Focusing recent increment of cancers metastasis to bone, we studied anionic Pt(II) complexes involving phosphate like group as LG and its affinity to hydroxyapatite (HA, C_<10>(PO_4)_6(OH)_2,) because HA is inorganic component of bone.Pt(DA)(LG) complexes (DA=(NH_3)_2, dach; LG=methylenediphosphonate (MDP), pyrophosphate (PP), inositolhexakisphosphate (IP6) were prepared from corresponding Pt(DA)I_2 by treatment of Ag^+ through chelate effect. Crystal structure of Pt(dach)(MDP) showed 2N(NH_2) and 2O(PO_3) coordination to Pt(II). These Pt(II) complexes were stable for hydrolysis in water and showed short half live time (t_<1/2>) in acidic solution. The crystal structure of Pt(dach)(MDP)-oligo DNA adduct revealed the monodentate coordination of Pt(dach) to guanine N7 and removal of MDP as LG. The typical property of these Pt(II) complexes was the excellent adsorption to HA, while cisplatin and carboplatin showed low adsorption. The adsorption fits Langmuir plot and its adsorption constant K depends on the number of P, so from the view of the adsorption the Pt(DA)(IP6) complexes were distinguished.Pt(DA)(LG) exhibited (1) new interaction mode with DNA; (2) good in vitro assay results; (3) good adsorption to HA.

临床抗癌Pt（II）络合物如顺铂、卡铂和奥沙利铂通常由2N和2Cl或2 O（羧酸根）作为供体原子组成。这些被称为“离去基团（LG）”的Cl和O基团被认为不太重要，因为抗癌Pt（II）药物在LG从Pt（II）配位解离后攻击DNA碱基。近年来，LG作为药物传递系统（DDS）的一种工具被广泛研究。针对近年来肿瘤骨转移的研究进展，我们研究了含类磷酸基团的阴离子Pt（II）配合物LG及其与羟基磷灰石（HA，C_<10>（PO_4）_6（OH）_2）的亲和性，因为HA是骨的无机成分。（DA=（NH_3）_2，dach; LG=亚甲基二膦酸盐（MDP），焦磷酸盐（PP），以Pt（DA）I_2为原料，通过螯合作用与Ag^+反应，合成了肌醇六磷酸（IP 6）。Pt（dach）（MDP）的晶体结构表明Pt（II）与2N（NH_2）和2 O（PO_3）配位。这些配合物在水中水解稳定，在酸性溶液中半衰期（t1/2）短。Pt（dach）（MDP）-寡聚DNA加合物的晶体结构显示Pt（dach）与鸟嘌呤N7的单齿配位和MDP以LG形式被去除。这些Pt（II）配合物的典型性质是对HA具有良好的吸附，而顺铂和卡铂表现出较低的吸附。吸附符合Langmuir曲线，吸附常数K与P的个数有关，因此从吸附角度区分了Pt（DA）（IP 6）配合物，Pt（DA）（LG）表现出（1）与DNA新的作用模式;（2）良好的体外测定结果;（3）对HA有良好的吸附。

项目成果

π-π Stacking assisted binding of aromatic amino acids by copper(II)-aromatic diimine complexes. Effects of ring substituents on ternary complex stability

π-π堆积辅助铜(II)-芳香族二亚胺络合物对芳香酸氨基的结合。环取代基对三元络合物稳定性的影响。

• 发表时间: 2007
• 期刊: Dalton 2007
• 作者: T.Yajima;R.Takamido;Y.Shimazaki;A.Odani;Y.Nakabayashi;O.Yamauchi
• 通讯作者: O.Yamauchi

Al(III)-binding ability of an octapeptide and its phosphorylated derivative.

八肽及其磷酸化衍生物的 Al(III) 结合能力。

• 发表时间: 2006
• 期刊: Journal of Inorganic Biochemistry 100・3
• 作者: Hollender;Dominik;Karoly-Lakatos;Andrea;Forgo;Peter;Koertvelyesi;Tamas;Dombi;Gyoergy;Majer;Zsuzsa;Hollosi;Miklos;Kiss;Tamas;Odani;Akira
• 通讯作者: Akira

The Methoxysubstituted TQEN Family of Fluorescent Zinc Sensors

甲氧基取代 TQEN 系列荧光锌传感器

• 发表时间: 2006
• 期刊: Inorg. Chem. 45
• 作者: M.Obata;N.Araki;M.Nakai;M.Gottschaldt;Y.Mikata;Y.Mikata
• 通讯作者: Y.Mikata

Co2(CO)8-catalyzed intramolecular hetero-Pauson-Khand reaction of alkynecarbodiimide: synthesis of (+/-)-physostigmine.

• DOI: 10.1021/ol052562z
• 发表时间: 2006-01
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: C. Mukai;T. Yoshida;M. Sorimachi;A. Odani

Ternary Cu(II) complexes, Cu(H(-1)L)(ACys-) and Cu(H(-2)L)(ACys-); L = peptides, ACys- = N-acetyl-cysteinate. Analogous complexes to the intermediates in the transport of Cu(II) from Cu(H(-2)L) to cysteine.

• DOI: 10.1016/j.jinorgbio.2005.11.017
• 发表时间: 2006-03
• 期刊: Journal of inorganic biochemistry
• 影响因子: 3.9
• 作者: A. Hanaki;Y. Funahashi;A. Odani