Abstract
Two modified glycosides--digoxin and proscillaridin A conjugated to a generation 3 of polyamidoamine dendrimer (G3 PAMAM-NH2) were evaluated as DNA topoisomerase II inhibitors. The ability of these compounds (PAMAM-Dig and PAMAM-Prosc) to inhibit topoisomerase I and II activity was quantified by measuring the action on supercoiled DNA substrate as a function of increasing concentration of the test compounds by the use of agarose gel electrophoresis. The obtained results suggest that a conjugation of the modified glycosides with G3 PAMAM-NH2 significantly improved the ability of the parent compounds to an inhibition of DNA topoisomerases.
MeSH terms
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Antigens, Neoplasm / chemistry
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Antigens, Neoplasm / metabolism
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DNA Topoisomerases, Type I* / chemistry
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DNA Topoisomerases, Type I* / metabolism
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DNA Topoisomerases, Type II / chemistry
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DNA Topoisomerases, Type II / metabolism
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DNA, Superhelical / metabolism
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DNA-Binding Proteins / antagonists & inhibitors*
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / metabolism
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Dendrimers / chemistry
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Dendrimers / pharmacology*
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Digoxin / chemistry
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Digoxin / pharmacology*
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Dose-Response Relationship, Drug
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Electrophoresis, Agar Gel
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Humans
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Molecular Structure
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Proscillaridin / chemistry
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Proscillaridin / pharmacology*
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Structure-Activity Relationship
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Topoisomerase Inhibitors / chemistry
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Topoisomerase Inhibitors / pharmacology*
Substances
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Antigens, Neoplasm
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DNA, Superhelical
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DNA-Binding Proteins
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Dendrimers
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G3 PAMAM-NH2 dendrimer-modified digoxin
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G3 PAMAM-NH2 dendrimer-modified proscillaridin A
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Topoisomerase Inhibitors
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Digoxin
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DNA Topoisomerases, Type I
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TOP1 protein, human
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DNA Topoisomerases, Type II
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Proscillaridin