Abstract
Three series of indeno[1,2-c]isoquinolines bearing a ferrocenyl entity were synthesized and evaluated for DNA interaction, topoisomerase I and II inhibition, and cytotoxicity against breast human cancer cell lines. In the first and second series, the ferrocenyl scaffold was inserted as a linker between the two nitrogen atoms. In the last series, it was introduced at the end of the carbon chain. The present study showed that the ferrocenyl entity enhanced the topoisomerase II inhibition. Most compounds showed a potent growth inhibitory effect on MDA-MB-231 cell line with the IC50 in μM range.
Keywords:
Cytotoxicity; Drug binding; Ferrocene; Indenoisoquinoline; Topoisomerase II inhibitor.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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 Proliferation / drug effects
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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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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Ferrous Compounds / chemical synthesis*
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Ferrous Compounds / chemistry
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Ferrous Compounds / pharmacology*
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Humans
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Inhibitory Concentration 50
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Isoquinolines / chemical synthesis*
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Isoquinolines / chemistry
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Isoquinolines / pharmacology*
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Molecular Structure
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Structure-Activity Relationship
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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*
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Tumor Cells, Cultured
Substances
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Antigens, Neoplasm
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Antineoplastic Agents
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DNA-Binding Proteins
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Ferrous Compounds
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Isoquinolines
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Topoisomerase II Inhibitors
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ferrocenyl indeno(1,2-c)isoquinoline
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DNA Topoisomerases, Type II