Prodrug activation by 4,4’-bipyridine-mediated aromatic nitro reduction

作者：Qing Wang, Yikang Song, Shuowei Yuan, Yaoji Zhu, Wen‐Jing Wang, Ling Chu · 发表于：Nature Communications · 年份：2024 · DOI：10.1038/s41467-024-52604-y · 被引用次数：20 · 研究领域：Nanomaterials for catalytic reactions、Asymmetric Hydrogenation and Catalysis、Adenosine and Purinergic Signaling

Unleashing prodrugs through nitro-reduction is a promising strategy in cancer treatment. In this study, we present a unique bioorthogonal reaction for aromatic nitro reduction, mediated by 4,4‘-bipyridine. The reaction is a rare example of organocatalyst-mediated bioorthogonal reaction. This bioorthogonal reaction demonstrates broad substrate scope and proceeds at low micromolar concentrations under biocompatible conditions. Our mechanistic study reveals that water is essential for the reaction to proceed at biorelevant substrate concentrations. We illustrate the utility of our reaction for controlled prodrug activation in mammalian cells, bacteria, and mouse models. Furthermore, a nitro-reduction-annulation cascade is developed for the synthesis of indole derivatives in living cells. Releasing prodrugs through nitroreduction is a promising strategy in cancer treatment. In this study, the authors present a 4,4‘-bipyridine-mediated bioorthogonal aromatic nitro reduction for activation of nitro prodrugs.