Potent Anticancer Efficacy of First‐In‐Class Cu II and Au III Metaled Phosphorus Dendrons with Distinct Cell Death Pathways

Liang Chen (1, 2) , Yu Fan (1) , Jieru Qiu (2) , Regis Laurent (2) , Jin Li (1) , Jérôme Bignon (3) , Serge Mignani (1, 4, 5) , Anne-Marie Caminade (2) , Xiangyang Shi (1, 5) , Jean Pierre Majoral (2)

1 CCEB - College of Chemistry, Chemical Engineering and Biotechnology, Donghua University
2 LCC - Laboratoire de chimie de coordination
3 ICSN - Institut de Chimie des Substances Naturelles
4 LCBPT - UMR 8601 - Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques
5 Centro de Química da Madeira

First-in-class CuII and AuIII metaled phosphorus dendrons were synthesized and showed significant antiproliferative activity against several aggressive breast cancer cell lines. The data suggest that the cytotoxicity increases with reducing length of the alkyl chains, whereas the replacement of CuII with AuIII considerably increases the antiproliferative activity of metaled phosphorus dendrons. Very interestingly, we found that the cell death pathway is related to the nature of the metal complexed by the plain dendrons. CuII metaled dendrons showed a potent caspase-independent cell death pathway, whereas AuIII metaled dendrons displayed a caspase-dependent apoptotic pathway. The complexation of plain dendrons with AuIII increased the cellular lethality versus dendrons with CuII and promoted the translocation of Bax into the mitochondria and the release of Cytochrome C (Cyto C).

Mots clés: Antiproliferation; Apoptosis; Dendrimers; Dendrons; Fluorescent probes; Imaging agents

Domaines: Chimie de coordination

Liang Chen, Yu Fan, Jieru Qiu, Regis Laurent, Jin Li, et al.. Potent Anticancer Efficacy of First‐In‐Class Cu II and Au III Metaled Phosphorus Dendrons with Distinct Cell Death Pathways. Chemistry - A European Journal, 2020, 26 (26), pp.5903-5910. ⟨10.1002/chem.202001014⟩. ⟨hal-02623761⟩