Using bio-orthogonally catalyzed lethality strategy to generate mitochondria-targeting anti-tumor metallodrugs in vitro and in vivo.

ABSTRACT: Synthetic lethality was proposed nearly a century ago by geneticists and recently applied to develop precision anti-cancer therapies. To exploit the synthetic lethality concept in the design of chemical anti-cancer agents, we developed a bio-orthogonally catalyzed lethality (BCL) strategy to generate targeting anti-tumor metallodrugs both in vitro and in vivo. Metallodrug Ru-rhein was generated from two non-toxic species Ru-N₃ and rhein-alkyne via exclusive endogenous copper-catalyzed azide alkyne cycloaddition (CuAAC) reaction without the need of an external copper catalyst. The non-toxic species Ru-arene complex Ru-N₃ and rhein-alkyne were designed to perform this strategy, and the mitochondrial targeting product Ru-rhein was generated in high yield (>

SUBMITTER: Xue X 

PROVIDER: S-EPMC8433091 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature