一系列α-杂环-N4-取代的硫代缩氨基脲及其铜(II)配合物的金属化在拓扑异构酶 IIα 抑制和增殖活性中的作用。
Role of metalation in the topoisomerase IIα inhibition and antiproliferation activity of a series of α-heterocyclic-N4-substituted thiosemicarbazones and their Cu(II) complexes.
机构信息
Department of Radiology and the Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, United States.
出版信息
J Med Chem. 2011 Apr 14;54(7):2391-8. doi: 10.1021/jm101532u. Epub 2011 Mar 10.
Abstract
The topoisomerase-IIα inhibition and antiproliferative activity of α-heterocyclic thiosemicarbazones and their corresponding copper(II) complexes have been investigated. The Cu(II)(thiosemicarbazonato)Cl complexes were shown to catalytically inhibit topoisomerase-IIα at concentrations (0.3-7.2 μM) over an order of magnitude lower than their corresponding thiosemicarbazone ligands alone. The copper complexes were also shown to inhibit the proliferation of breast cancer cells expressing high levels of topoisomerase-IIα (SK-BR-3) at lower concentrations than cells expressing lower levels of the enzyme (MCF-7).
摘要
已经研究了α-杂环硫代缩氨基脲及其相应的铜（II）配合物的拓扑异构酶-IIα 抑制和抗增殖活性。结果表明，Cu（II）（硫代缩氨基脲）Cl 配合物在浓度（0.3-7.2 μM）下可催化抑制拓扑异构酶-IIα，其浓度比相应的硫代缩氨基脲配体单独使用时低一个数量级。还表明铜配合物在较低浓度下抑制表达高水平拓扑异构酶-IIα（SK-BR-3）的乳腺癌细胞的增殖，低于表达较低水平酶的细胞（MCF-7）。
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Role of metalation in the topoisomerase IIα inhibition and antiproliferation activity of a series of α-heterocyclic-N4-substituted thiosemicarbazones and their Cu(II) complexes.一系列α-杂环-N4-取代的硫代缩氨基脲及其铜(II)配合物的金属化在拓扑异构酶 IIα 抑制和增殖活性中的作用。
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