Abbott - Medicinal chemistry and synthetic organic chemistry
Medicinal chemistry involves the design, synthesis and development of the molecules we need in order to understand, prevent and treat disease.
We use synthetic organic chemistry to make novel compounds and then test them in biological assays, which are either undertaken in our lab or by collaborators, in order to study the structure-activity relationships of how the compounds interact with the target.
Developing novel antibacterial agents to inhibit targets that have not previously been studied in bacteria is currently an important focus of our group.
Other projects are working towards new treatments for malaria, cardiomyopathy and motor neurone disease.
We are particularly interested in small molecule inhibitors of protein kinases and cyclic nucleotide phosphodiesterases, such as PI3-kinase, JAK, PDK1, PKA, PDE2 and PDE3.
We have also been involved in the development and application of peptide nucleic acid (PNA) technology in the early detection and treatment of disease.
Research areas
Fragment-based drug design of inhibitors of N.meningitidis DsbD
Multi-drug resistant bacteria represent a significant public health threat. It is critical to develop new ways to treat bacterial infections which target pathways different to those used by current drugs.
Periplasmic Disulfide Bond (Dsb) forming enzymes catalyse the oxidative folding of many toxins and surface proteins required for virulence in a range of pathogenic bacteria including meningitis and gonorrhoea. We are working to develop initial hits obtained from a screened library into higher-affinity ligands using the approach of fragment-based drug design (FBDD).
Development of novel treatments for cardiac arrhythmia and hypertension
Beta-blockers such as propranolol are commonly used to treat cardiac arrhythmia and hypertension but have serious side effects; patients have a 5-year survival rate of 50%. New therapeutics for the treatment of these heart conditions are urgently needed.
We are currently studying the ability of four compound classes to prevent induction of the pro-apoptotic Bim protein but at the same time not affect CREB phosphorylation, a discovery which may be the key to the development of successful cardiac drug treatments.
Exploring the inhibition of PKA as a new therapeutic target for malaria
Malaria causes much damage to the health of the developing world. Protein kinase A (PKA) is important in the life cycle of the malaria parasite and may be an attractive target for inhibition. We are synthesising analogues of the isoquinoline compound A4 to test against this kinase and obtain SAR information, in order to develop a potent inhibitor to learn more about the role of PKA and its usefulness as a potential drug for malaria.
Structure-activity relationships of novel antibacterial inhibitors of DHDPS
Dihydrodipicolinate synthase (DHDPS) catalyses the first step of the biosynthetic pathway which produces meso-DAP. It is essential for bacterial survival and so represents a new target for antibacterial drugs. A number of low MW molecules have been identified from a compound library using high throughput screening and we wish to further explore the structure-activity relationships of these hits through the synthesis of analogues.
Rebecca Christoff Chamodi Gardhi Catherine Meister Benjamin Richards Monica Nguyen
Honours student
Joshua Mullen
Patents
Substituted sulfonyl hydrazides as inhibitors of lysine biosynthesis via the diaminopimelate pathway: Australian Provisional Patent Application 1079445
Heterocyclic compounds as inhibitors of lysine biosynthesis via the diaminopimelate pathway: Australian Provisional Patent Application 1079451
Group leader