Targeting translation: a promising strategy for anticancer metallodrugs

[Display omitted] •Coordination and organometallic compounds as proteosynthesis inhibitors are summarized.•An overview on compounds for which mechanistic data was obtained is provided.•A preliminary relationship between structure of the complex and the mode of action has been established.•Attention...

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Veröffentlicht in:Coordination chemistry reviews 2021-11, Vol.446, p.214129, Article 214129
Hauptverfasser: Ortega, Enrique, Vigueras, Gloria, Ballester, Francisco José, Ruiz, José
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Sprache:eng
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Zusammenfassung:[Display omitted] •Coordination and organometallic compounds as proteosynthesis inhibitors are summarized.•An overview on compounds for which mechanistic data was obtained is provided.•A preliminary relationship between structure of the complex and the mode of action has been established.•Attention to photocaged prodrugs is also paid. Translation is the most energy-consuming activity within cells. Due to metabolic demands and high proliferation, cancer cells require elevated rates of protein synthesis, thus providing a therapeutic window to selectively eliminate them. Among potential anticancer agents, metallodrugs have arisen as an important class of chemotherapeutics due to the variety of possible molecular architectures and multiple coordination and redox states these compounds can achieve. Inorganic medicinal drug discovery has experimented remarkable advances over the past decades with current metal-based representatives undergoing clinical trials for cancer disease. Herein, we summarize the status of research on metal compounds targeting proteosynthesis. This review starts with a brief overview on protein synthesis as an anticancer target that is followed by an introduction to translational control in cancer cells and the importance of this process for cancer therapy. Metal-based chemotherapeutic agents are classified according to the transition metal, accompanied by a discussion on their mode of action interfering with protein synthesis and recapitulating both preclinical and clinical data.
ISSN:0010-8545
1873-3840
DOI:10.1016/j.ccr.2021.214129