Abstract
Anaerobic reduction of anticancer prodrugs is a promising route to achieve targeting and selectivity in anticancer drug design. Most reductive prodrug activations involve simple electron transfer from a flavoprotein and are not amenable to specific targeting. Here, we report that the N-oxide AQ4N is reduced by a nitric oxide synthase. This reduction involves interaction with the heme iron atom in the active site and is thus subject to specific protein constraints.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Anaerobiosis
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Anthraquinones / chemistry
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Anthraquinones / metabolism*
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Binding Sites
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Cytochrome P-450 CYP3A / metabolism
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Heme / chemistry
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Nitric Oxide Synthase / metabolism*
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Nitric Oxide Synthase Type II / metabolism
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Oxidation-Reduction
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Prodrugs / metabolism*
Substances
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Anthraquinones
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Prodrugs
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Heme
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AQ4N
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NOS2 protein, human
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Cytochrome P-450 CYP3A
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CYP3A4 protein, human