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).
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Antigens, Neoplasm / metabolism
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Copper / chemistry*
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DNA Topoisomerases, Type II / metabolism
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DNA-Binding Proteins / antagonists & inhibitors*
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DNA-Binding Proteins / metabolism
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Gene Expression Regulation, Neoplastic
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Heterocyclic Compounds / chemistry*
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Humans
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Inhibitory Concentration 50
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Nitrogen / chemistry*
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Organometallic Compounds / chemical synthesis
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Organometallic Compounds / chemistry*
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Organometallic Compounds / pharmacology*
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Structure-Activity Relationship
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Thiosemicarbazones / chemistry*
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Topoisomerase II Inhibitors / chemical synthesis
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Topoisomerase II Inhibitors / chemistry
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Topoisomerase II Inhibitors / pharmacology
Substances
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Antigens, Neoplasm
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Antineoplastic Agents
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DNA-Binding Proteins
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Heterocyclic Compounds
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Organometallic Compounds
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Thiosemicarbazones
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Topoisomerase II Inhibitors
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Copper
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DNA Topoisomerases, Type II
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Nitrogen