From the design of innovative Ti‐Pt heterometallic complexes to the development of highly anti‐proliferative water‐soluble cationic titanocenes

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Trommenschlager, Audrey | Mabrouk, Nesrine | Racoeur, Cindy | Godard, Amélie | Balan, Cédric | Dubrez, Laurence | Bettaieb, Ali | Husson, Jerôme | Le Gendre, Pierre | Paul, Catherine | Bodio, Ewen

Edité par CCSD ; Wiley-VCH Verlag -

International audience. 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.

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