Our research group has a strong interest in synthesis and the medicinal chemistry of Main Group and Lanthanoid elements, with an emphasis on drug discovery and the design of new theranostic agents.
We are very interested in exploiting the unique properties of boron and gadolinium in cutting-edge cancer therapies, and their incorporation into unique molecular scaffolds for binding to important biological receptors or as new biological fluorophores.
Our research has received funding from organizations including the Australian Research Council, The Prostate Cancer Foundation of Australia, Cure Cancer Australia Foundation and The National Breast Cancer Foundation.
The 5-year survival rate for patients afflicted with aggressive and intractable malignant brain tumours (gliomas) is very poor (< 4%). We have incorporated Gd3+ ions into mitochondrial-targeting agents in order to localise the metal ion near a critical sub-cellular organelle for application in cutting-edge binary cancer therapies such as photon activation therapy (PAT) and neutron capture therapy (NCT).
We have already demonstrated substantial and selective brain tumour tumour cell destruction in the presence of a prototype Gd agent and synchrotron X-ray photons, the first time that GdPAT experiments have ever been conducted in Australia using the Imaging and Medical Beamline at the Australian Synchrotron.
The use of Gd agents to target tumour cell mitochondria would open up new vistas in binary cancer therapies, with potential tumour imaging applications in MRI.
Boron-based drugs are increasingly being investigated in many disease categories, with several pharmaceutical companies (e.g. GSK, Anacor (now Pfizer), and Takeda) dramatically expanding their boron research programs in recent years in the quest for novel drug candidates, e.g. Velcade®(bortezomib) which is used in the treatment of multiple myeloma.
Almost all boron drugs investigated to date, however, are based upon boronic acids and boronate esters. In contrast, polyhedral boron clusters known as carboranes have rarely been exploited as new types of robust, structural frameworks in medicinal chemistry, and their use as enzyme inhibitors or receptor agonists/antagonists is largely underdeveloped. We are currently investigating the use of carboranes as unique frameworks in new drugs for the diagnosis and treatment of aggressive and intractable cancers such as malignant gliomas.
Current biological targets include: histone deacetylases (HDACs), indoleamine-2,3-dioxygenase 1 (IDO1), the 18 kDa Translocator protein (TSPO), and the P2X7 receptor.
Fluorescently-labelled molecules are invaluable tools in microscopy. There is a continuing need to develop new fluorophores, particularly those that emit in the near-IR, and those in which chemical properties can be easily tuned.
This project involves the rational design and synthesis of new boron-containing fluorophores, their photophysical characterisation and biological studies (with A/Prof. Liz New). For example, we have recently developed a new biological stain for lipids. Our novel carborane-coumarin selectively stains cellular lipid droplets in live adipocytes due to its unique solvent-dependent photophysical properties and lipophilic nature.
he combination of these properties ensure its superior selectivity toward lipid droplets in cellulo over analogous organic (phenyl) derivatives and commonly-used dyes such as Nile Red.