Abstract
A number of 1,4- and 2,6-difunctionalized amidoanthracene-9, 10-diones have been prepared. We have examined their in vitro cytotoxicity in several tumor cell lines and their ability to inhibit the telomere-addition function of the human telomerase enzyme together with their inhibition of the Taq polymerase enzyme. Compounds with -(CH2)2- side chains terminating in basic groups such as piperidine show inhibition of telomerase at telIC50 levels of 4-11 microM. These are thus among the most potent nonnucleoside telomerase inhibitors reported to date. Cytotoxicity levels in human tumor cell lines were at comparable levels for several compounds. Implications for amidoanthracene-9,10-dione telomerase inhibitors as potential anticancer agents are discussed.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anthraquinones / chemical synthesis*
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Anthraquinones / chemistry
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Anthraquinones / pharmacology
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Anthraquinones / toxicity
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / toxicity
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Cell Division / drug effects
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Cell Survival / drug effects
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Doxorubicin / toxicity
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Enzyme Inhibitors / toxicity
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Female
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Gene Amplification
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Humans
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Kinetics
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Mitoxantrone / toxicity
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Molecular Structure
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Ovarian Neoplasms
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Structure-Activity Relationship
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Taq Polymerase / antagonists & inhibitors
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Telomerase / antagonists & inhibitors*
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Telomere
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Tumor Cells, Cultured
Substances
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Anthraquinones
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Antineoplastic Agents
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Enzyme Inhibitors
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Doxorubicin
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Mitoxantrone
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Taq Polymerase
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Telomerase