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Journal of medicinal chemistry

Reductive heme-dependent activation of the n-oxide prodrug AQ4N by nitric oxide synthase.


PMID 18681417

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.