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Molecular Pharmacology

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Abstract

A search for potential antitumor agents: biological effects and DNA binding of a series of anthraquinone derivatives.

G Palù, M Palumbo, C Antonello, G A Meloni and S Marciani-Magno
Molecular Pharmacology February 1986, 29 (2) 211-217;
G Palù
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M Palumbo
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C Antonello
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G A Meloni
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S Marciani-Magno
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Abstract

In an effort to establish a relationship between mechanism of binding and affinity to DNA, cytotoxic activity, and genotoxic activity, we have studied four new anthracenedione derivatives bearing charged side chain groups at various positions of the polycyclic aromatic system. Cytotoxicity, genotoxicity, and thermodynamic DNA binding parameters were shown to be directly related, indicating the polynucleotide as an important target for drug action, rather than a minor, subterminal interacting site. This finding was further supported by the observation of extensive anthraquinone accumulation occurring in the nuclear compartment. The relative binding affinities of the drugs are discussed in terms of nature and position of side-chain substituents. Different binding modes were found: three compounds intercalate into the nucleic acid double helix, and one interacts with the exterior of the macromolecule. The biological results suggest that the mode of complex formation plays a less relevant role than DNA binding efficiency.

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Molecular Pharmacology
Vol. 29, Issue 2
1 Feb 1986
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Abstract

A search for potential antitumor agents: biological effects and DNA binding of a series of anthraquinone derivatives.

G Palù, M Palumbo, C Antonello, G A Meloni and S Marciani-Magno
Molecular Pharmacology February 1, 1986, 29 (2) 211-217;

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Abstract

A search for potential antitumor agents: biological effects and DNA binding of a series of anthraquinone derivatives.

G Palù, M Palumbo, C Antonello, G A Meloni and S Marciani-Magno
Molecular Pharmacology February 1, 1986, 29 (2) 211-217;
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