Abstract
The reactivation of telomerase activity in most cancer cells supports the concept that telomerase is a relevant target in oncology, and telomerase inhibitors have been proposed as new potential anticancer agents. The telomeric G-rich single-stranded DNA can adopt an intramolecular G-quadruplex structure in vitro, which has been shown to inhibit telomerase activity. The C-rich sequence can also adopt a quadruplex (intercalated) structure (i-DNA). Two acridine derivatives were shown to increase the melting temperature of the G- quadruplex and the C-quadruplex at 1 microM dye concentration. The increase in Tm value of the G-quadruplex was associated with telomerase inhibition in vitro. The most active compound, "BisA", showed an IC(50) value of 0.75 microM in a standard TRAP assay.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acridines / chemistry
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Acridines / metabolism*
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Binding Sites
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Bridged-Ring Compounds / chemistry
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Bridged-Ring Compounds / metabolism*
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Cytosine / chemistry
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DNA / chemistry
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DNA / metabolism*
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DNA, Single-Stranded / chemistry
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Dimerization
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / metabolism*
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Fluorescence
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Fluorescent Dyes / metabolism
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G-Quadruplexes
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Guanine / chemistry
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Humans
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Kinetics
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Ligands
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Nucleic Acid Conformation
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Oligonucleotides / chemistry
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Rhodamines / metabolism
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Spectrometry, Fluorescence / methods
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Telomerase / metabolism*
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Telomere / chemistry
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Temperature
Substances
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Acridines
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BisA compound
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Bridged-Ring Compounds
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DNA, Single-Stranded
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Enzyme Inhibitors
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Fluorescent Dyes
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Ligands
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MonoA compound
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Oligonucleotides
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Rhodamines
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Guanine
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Cytosine
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DNA
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Telomerase