Resumen de Coordination, organometallic and supramolecular chemistry approaches to the design of metal-based cytotoxic agents
The discovery of cisplatin and its successful use as chemotherapeutic agent have encouraged the development of metal-based anticancer molecules. The present doctoral research project includes three different chemistry approaches to design new metal-based cytotoxic compounds. Coordination, organometallic and supramolecular chemistry have been used to successfully develop three families of compounds with highly promising biological properties.
Copper(II) coordination compounds of various nuclearities have been prepared from new Schiff-base ligands. The complexes strongly interact with DNA without cleaving it and exhibit notable cytotoxicities against various murine and human cancer cell lines. Organometallic ruthenium(II)-arene compounds containing a monophosphane PR3 ligand have been obtained, which show remarkable cytotoxicites against a wide panel of human cancer cells, so as very interesting antimetastatic properties. Structureactivity relationship studies have been carried out, which illustrated the great potential (and versatility) of this family of molecules, whose biological properties can be finetuned by the selection of the different ligands bound to the metal.
A new family of supramolecular compounds has been developed with the objective to target the DNA major groove or/and stabilize non-conventional DNA structures, for instance the three-way junction (3WJ). The series of iron(III) metallohelicates prepared exhibit groove-binding properties but are not capable of stabilizing the 3WJ. Some of these helical complexes show interesting cytotoxic properties and one of them can even induce cell apoptosis.
