Prodrug activation by 4,4'-bipyridine-mediated aromatic nitro reduction.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
05 Oct 2024
Historique:
received: 17 10 2023
accepted: 16 09 2024
medline: 6 10 2024
pubmed: 6 10 2024
entrez: 5 10 2024
Statut: epublish

Résumé

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.

Identifiants

pubmed: 39368987
doi: 10.1038/s41467-024-52604-y
pii: 10.1038/s41467-024-52604-y
doi:

Substances chimiques

Prodrugs 0
4,4'-bipyridyl X4O2OD61CB
Indoles 0
Pyridines 0
Nitro Compounds 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

8643

Subventions

Organisme : Tsinghua University (THU)
ID : Dushi plan

Informations de copyright

© 2024. The Author(s).

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Auteurs

Qing Wang (Q)

School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China.

Yikang Song (Y)

School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China.

Shuowei Yuan (S)

School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China.

Yaoji Zhu (Y)

School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China.

Wenjing Wang (W)

School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China.

Ling Chu (L)

School of Pharmaceutical Sciences MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology Tsinghua University, Beijing, 100084, China. lingchu@mail.tsinghua.edu.cn.
Beijing Frontier Research Center for Biological Structure, Tsinghua University, Beijing, 100084, China. lingchu@mail.tsinghua.edu.cn.

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