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A Bis-Chelating / Ligand for the Synthesis of Heterobimetallic Platinum(II)/Rhenium(I) Complexes: Tools for the Optimization of a New Class of Platinum(II) Anticancer Agents
Authors:Dr. Benoît Bertrand  Dr. Candice Botuha  Jérémy Forté  Dr. Héloïse Dossmann  Dr. Michèle Salmain
Affiliation:CNRS, Institut Parisien de Chimie Moléculaire (IPCM), Sorbonne Université, 75005 Paris, France
Abstract:The two independent and urn:x-wiley:09476539:media:chem202001752:chem202001752-math-0003 coordination sites of a newly synthesized bis[2-(hydroxyphenyl)-1,2,4-triazole] platform have been exploited to prepare four monometallic neutral ()PtII complexes carrying DMSO, pyridine, triphenylphosphine, or N-heterocyclic carbene as the fourth ligand. Then, the second urn:x-wiley:09476539:media:chem202001752:chem202001752-math-0004 coordination site was used to introduce an IR-active rhenium tricarbonyl entity, affording the four corresponding heterobimetallic neutral PtII/ReI complexes, as well as a cationic PtII/ReI derivative. X-ray crystallographic studies showed that distortion of the organic platform occurred to accommodate the coordination geometry of both metal centers. No ligand exchange or transchelation occurred upon incubation of the PtII complexes in aqueous environment or in the presence of FeIII, respectively. The antiproliferative activity of the ligand and complexes was first screened on the triple-negative breast cancer cell line MDA-MB-231. Then, the IC50 values of the most active candidates were determined on a wider panel of human cancer cells (MDA-MB-231, MCF-7, and A2780), as well as on a nontumorigenic cell line (MCF-10A). Low micromolar activities were reached for the complexes carrying a DMSO ligand, making them the first examples of highly active, but hydrolytically stable, PtII complexes. Finally, the characteristic mid-IR signature of the {Re(CO)3} fragment in the Pt/Re heterobimetallic complexes was used to quantify their uptake in breast cancer cells.
Keywords:cancer  drug design  ligand design  platinum  rhenium
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