欢迎您！东篱公司
退出
-
申报数据库
-
立项数据库
-
成果数据库
-
项目获奖数据库
位置：立项数据库 > 立项详情页
中文摘要：
本项目以拓扑异构酶I（TopoI）为靶点，突破基于喜树碱类化合物构效关系设计Topo I抑制剂的束缚，以合成的对称和不对称两大类N,N'-双取代草酰胺为桥基，定向合成和表征了一百多种过渡金属多核配合物，并用X-单晶衍射测定和解析了61个桥联多核配合物的晶体结构，揭示了配合物体系中氢键和各种堆积等弱相互作用对构筑超分子的影响，这些化合物均为国际同类化合物的首例；从细胞和动物水平上系统研究了这些配合物对Topo I的抑制作用和抗癌活性；通过对其结构和抑制Topo I活性及抗癌活性的对比分析，探讨了此类化合物的构效关系；首次发现5个双核和一个四核铜(II)以及一个双核钒(II)配合物具有抑制Topo I活性和抗癌活性。其中，双核钒配合物对Topo I的抑制半数作用剂量(IC50)为8.6 μM，其作用强于羟基喜树碱(OPT)；体外和体内试验证明该配合物具有抗癌活性；首次发现了3种四核铜(II)配合物通过水解磷酸二酯键对DNA有直接切割作用，其最低有效切割浓度达到12.5μM。研究工作已在SCI收录的学术刊物上发表论文29篇，为靶向Topo I新结构类型抗癌药物的合理设计提供了新思路。
结论摘要：
英文主题词Topoisomerase I；Anticancer activity；Camptothecin；Binuclear complexes；Structure-activity relationship
成果综合统计
期刊论文
会议论文
专利
获奖
著作
期刊论文
Synthesis, crystal structure, antibacterial activities, and DNA-binding studies of a new μ-oxamido-b
Synthesis, crystal structure, cytotoxic activities and DNA-binding properties of new binuclear coppe
Synthesis, Crystal Structure and DNA binding Studies of bis(piperidinium)bis-(N,N,N',N'-tetramethyle
[Cu4(H2O)4(dmapox)2(btc)]n·10nH2O: The first two-dimensional polymeric copper(II) complex with bridg
Bis[ μ3-cis-N-(2-aminopropyl)-N'-(2-carboxylatophenyl)oxamidato(3-)]-bis(2,2'-bipyridine)dichloridot
One-dimensional copper(II) polymer with bridging μ-trans-oxamidate and thiocyanate ligands: Synthesi
A new two-dimensional polymeric copper(II) complex bridge both by oxamidate and azide groups: synthe
Two-dimensional supramolecular architecture of oxamido-bridged binuclear Copper(II) complex Cu-2(oxe
Aqua(2,2 '-diamino-4,4 '-bi-1,3-thiazole-kappa N-2,N ')(oxydiacetato-kappa O-3,O ',O '')cobalt(II) t
Aqua-2 kappa O-mu-{N,N '-bis[2-(dimethylamino)ethyl]oxamidato(2-)}-1 kappa O-2,O ': 2 kappa N-4,N ',
One-dimensional copper(II) coordination polymers bridged both by mu-trans-oxamidates and phenyldicar
Synthesis, crystal structures and DNA-binding properties of two new mononuclear copper(II) complexes
Synthesis, structural characterization and luminescent properties of a mixed valence hexavanadate cl
Synthesis, Structure and DNA Binding Properties of [Cu-2(heae)(SCN)(2)] n center dot nH(2)O the Firs
{mu-N,N '-Bis[2-(dimethylamino)ethyl]oxamidato(2-)-kappa N-6,N ',O ': N '',N ''',O}bis[(2,2 '-bipyri
A two-dimensional copper(II) polymer with bridging mu-trans-oxamidate and mu(2)-picrate ligands: Syn
Synthesis, crystal structure and DNA-binding study of a new Copper(II) complex containing mixed-liga
Synthesis, crystal structure, antibacterial assay and DNA binding activity of new binuclear Cu(II) c
相关项目
李延团的项目