Pincer-based heterobimetallic Pt(II)/Ru(II), Pt(II)/Ir(III) and Pt(II)/Cu(I) complexes: synthesis and evaluation antiproliferative properties

Benoit Bertrand (1, 2) , Geoffrey Gontard (1) , Candice Botuha (1, 2) , Michèle Salmain (1, 2)

1 IPCM - Institut Parisien de Chimie Moléculaire
2 CHEMBIO - Chemical Biology

Platinum pincer‐based complexes [(O^N^O)Pt(L)] (L = DMSO, pyridine, triphenylphosphine or 1,3‐dimethylbenzimidazol‐2‐ylidene) carrying an (N^N) coordination site were used as starting materials to synthesize a series of seven cationic heterobimetallic Pt(II)/Ru(II), Pt(II)/Ir(III), and Pt(II)/Cu(I) presenting a [(p‐cymene)RuCl]+, a [(Cp*)IrCl]+ (Cp* = η5‐pentamethylcyclopentadienyl), and a [(NHCiPr)Cu]+ {NHCiPr = 1,3‐bis(2,6‐diisopropylphenyl)imidazole‐2‐ylidene} moiety, respectively. The X‐ray structure of one of the bimetallic Pt(II)/Ir(III) complexes showed a distortion of the organic platform to accommodate the coordination geometry of both metal centers, as already observed for previous Pt(II)/Re(I) complexes. The antiproliferative activity of the complexes was first screened on the triple negative breast cancer cell line MDA‐MB‐231. Then the IC50 of the most active candidates was determined on a wider panel of human cancer cells (MDA‐MB‐231, MCF‐7 and A2780) as well as on a non‐tumorigenic cell line (MCF‐10A). The most toxic compound, namely the Pt(II)/Cu(I) heterobimetallic complex 4c, showed antiproliferative activity down to the nanomolar level.

Domaines: Chimie thérapeutique; Chimie de coordination

Benoit Bertrand, Geoffrey Gontard, Candice Botuha, Michèle Salmain. Pincer-based heterobimetallic Pt(II)/Ru(II), Pt(II)/Ir(III) and Pt(II)/Cu(I) complexes: synthesis and evaluation antiproliferative properties. European Journal of Inorganic Chemistry, 2020, 2020 (35), pp.3370-3377. ⟨10.1002/ejic.202000717⟩. ⟨hal-02948420⟩