Metal-based Chemical Entities: Opportunities in Chemical Biology and to Achieve Targeted Therapeutic Agents

My research interests concern mainly the study of the modes of action of metal compounds as anticancer agents and the development of novel metal-based chemical entities with possible biological applications. Besides synthetic inorganic chemistry and structural characterization of new metal complexes (mainly gold coordination and organometallic compounds), we strongly focus on an intensive biological evaluation of the new compounds as possible therapeutic agents, and on the investigation of their mechanisms of pharmacological activity and toxicity. To this aim, we have achieved target identification for different families of gold(I) and gold(III) complexes, including the membrane water channels aquaporins,[1] as well as proteins’ zinc finger domains.[2] Furthermore, novel applications for metal-based compounds and supramolecular scaffolds have been explored in various domains of chemical biology, bio-analytical chemistry and physiology. Here, I present recent results from our group representative of this interdisciplinary approach, which takes advantage of biophysical and analytical techniques coupled with pharmacological methods. Figure 1 – Non-covalent docking of a gold compound in an aquaporin channel, where it acts as an inhibitor. References[1] Martins A.P., Marrone A., Ciancetta A., Galán Cobo A., Echevarría M., Moura T.F., Re N., Casini A., G.Soveral, “Targeting aquaporin function: potent inhibition of aquaglyceroporin-3 by a gold-based compound”,PLoS One 2012, 7, pp. e37435.[2] Gold finger formation studied by high-resolution mass spectrometry and in silico methods, U. A. Laskay, C.Garino, Y. Tsybin, L. Salassa, A. Casini, Chem. Commun. 2015, 51, 1612-5.