Journal Article Ppublish
PubMed: 38749920 DOI: 10.1002/cbic.202400099
From the Design of Innovative Ti-Pt Heterometallic Complexes to the Development of Highly Anti-Proliferative Water-Soluble Cationic Titanocenes.
Chembiochem 25(19):e202400099
Authors: Audrey Trommenschlager, Nesrine Mabrouk, Cindy Racoeur, Amélie Godard, Cédric Balan, Laurence Dubrez, Ali Bettaïeb, Jérôme Husson, Pierre Le Gendre, Catherine Paul, Ewen Bodio
Affiliations
- Institut de Chimie Moléculaire de l'Université de Bourgogne (ICMUB UMR CNRS 6302), Université de Bourgogne, 21000, Dijon, France.
- Laboratoire d'Immunologie et Immunothérapie des Cancers (LIIC, EA7269) EPHE, PSL Research University, 75000, Paris, France, Université de Bourgogne, 21000, Dijon, France.
- LNC UMR1231, Institut National de la Santé et de la Recherche Médicale (Inserm), Université de Bourgogne, 21000, Dijon, France.
- Institut UTINAM UMR6213, Univ. de Franche-Comté, 25030, Besançon Cedex, France.
Abstract
Two innovative early/late Ti-Pt-heterobimetallic complexes were synthesized, characterized, and screened in cell-based assays using several human (SW480 and MDA-MB-231) and murine cancer cell lines (CT26 and EMT6) as well as a non-cancerous cell line (HMEC). The combination of the two metals - titanium(IV) and platinum (IV) - in a single molecule led to a synergistic biological activity (higher anti-proliferative properties than a mixture of each of the corresponding monometallic complexes). This study also investigated the benefits of associating a metal-free terpyridine moiety (with intrinsic biological activity) with a water-soluble titanocene fragment. The present work reveals that these combinations results in water-soluble titanocene compounds displaying an anti-proliferative activity down to the submicromolar level. One of these complexes induced an antitumor effect in vivo in CT26 tumor bearing BALB/C mice. The terpyridine moiety was also used to track the complex in vitro by multiphoton microscopy imaging.
MeSH
Cells, Biochemistry, Neoplasms, Cell Line