Research overview
Our research is focused on the synthesis, photochemistry and bio-activity of coordination or organometallic compounds employing a platinum group transition metal centre, most commonly ruthenium(II) or platinum(II), bound to organic ligands.
These compounds are of great interest in chemical biology and medicinal chemistry as they have coordination numbers greater than carbon’s limit of 4, well-developed synthetic pathways, extremely useful photochemical properties for assay development and possess at least one metal atom identifiable by mass spectrometry.
Our aim is to develop these molecules for use as cell imaging agents, tools for molecular biology and even therapeutic leads, particular within cancer research.
See below for current research projects.
Metallodrugs in combination therapy
Combination therapy employing drugs with complimentary mechanisms of action is one of the most successful treatment strategies for cancer. This research theme aims to develop metallocompounds for use in combination with PARP (poly ADP ribose polymerase) inhibitors (PARPi) for aggressive or drug-resistant cancers. Of special interest are Ruthenium(II) polypyridyl complexes (RPCs) that bind DNA by metallo-intercalation (the reversible insertion of a ligand between DNA base pairs), which act to stall DNA replication forks in rapidly-proliferating cancer cells without generating genotoxic double-strand break damage (see Sci. Rep. 2016). This biological activity results in PARPi drug synergy and renders triple-negative breast cancer cells hypersensitive to the FDA-approved Olaparib with minimal impact towards normal cells.
We propose that these identified synergistic drug combinations can: i) reduce the active dose of PARPi required for treatment and ii) expand the scope of PARPi to include a greater range of cancer types, including BRCA-proficient tumors. Together, we believe this approach can improve disease responses and overcome acquired or de novo drug resistance, a common issue with PARPi treatment.
Publications: ACS Chem Biol 2020, ChemMedChem 2020, Sci. Rep. 2023, J. Med Chem. 2023,