Abstract
A novel 2-(furan-2-yl)-4-(pyridin-2-yl)-5H-indeno[1,2-b]pyridin-5-one (TI-1-190) was synthesized using a simple microwave-assisted method and its mode of action was systematically characterized. It is a DNA intercalative human topoisomerase IIα catalytic inhibitor with much stronger activity and less DNA toxicity than etoposide, a topoisomerase II poison. TI-1-190 displays caspase 3-independent anticancer activity, unlike etoposide.
MeSH terms
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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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Apoptosis / drug effects
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Biocatalysis
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Caspase 3* / metabolism
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Cell Line, Tumor
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Cell Proliferation / drug effects
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DNA Topoisomerases, Type II / metabolism
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Humans
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Intercalating Agents / chemical synthesis
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Intercalating Agents / chemistry
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Intercalating Agents / pharmacology*
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MCF-7 Cells
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Molecular Structure
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Poly-ADP-Ribose Binding Proteins / antagonists & inhibitors*
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Poly-ADP-Ribose Binding Proteins / metabolism
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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*
Substances
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Antineoplastic Agents
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Intercalating Agents
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Poly-ADP-Ribose Binding Proteins
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Topoisomerase II Inhibitors
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Caspase 3
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DNA Topoisomerases, Type II
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TOP2A protein, human