Enamine N-Oxides: Synthesis and Application to Hypoxia-Responsive Prodrugs and Imaging Agents.

ABSTRACT: Tumor hypoxia induces the large-scale adaptive reprogramming of cancer cells, promoting their transformation into highly invasive and metastatic species that lead to highly negative prognoses for cancer patients. We describe the synthesis and application of a hypoxia-responsive trigger derived from previously inaccessible enamine N-oxide structures. Hypoxia-dependent reduction of this motif by hemeproteins results in the concomitant activation of a caged molecule and a latent electrophile. We exploit the former in a hypoxia-activated prodrug application using a caged staurosporine molecule as a proof-of-principle. We demonstrate the latter in in vivo tumor labeling applications with enamine-N-oxide-modified near-infrared probes. Hypoxia-activated prodrug development ha

SUBMITTER: Kang D 

PROVIDER: S-EPMC8155465 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature