Rational Optimisation of the Uptake of Metal-Based Anti-Cancer Agents by Tumours. In this project will develop an understanding of how anticancer drugs are taken up, distributed and modified in tumours. The information gathered will be of value to all those developing new anticancer drugs and we will then use it to develop new drugs that more selectively target tumours and therefore have reduced side effects. Successful development of less toxic anticancer agents would lead to less debilitating ....Rational Optimisation of the Uptake of Metal-Based Anti-Cancer Agents by Tumours. In this project will develop an understanding of how anticancer drugs are taken up, distributed and modified in tumours. The information gathered will be of value to all those developing new anticancer drugs and we will then use it to develop new drugs that more selectively target tumours and therefore have reduced side effects. Successful development of less toxic anticancer agents would lead to less debilitating treatment, more effective treatment, and an increase in the number of patients effectively treated. Effective anticancer drugs can also be very large income earners for Australia.Read moreRead less
Characterisation of two-pore domain potassium channels: structure-function studies of the M1-P1 loops of TASK channels. TWIK-related Acid Sensitive K+ (TASK) channels are members of the novel class of two-pore domain potassium channel family. They are potently inhibited by local anaesthetics and have been implicated as having important roles in many pathophysiological conditions such as heart arrythmias, stroke, epilepsy, breast and other cancers. The in depth structural and functional character ....Characterisation of two-pore domain potassium channels: structure-function studies of the M1-P1 loops of TASK channels. TWIK-related Acid Sensitive K+ (TASK) channels are members of the novel class of two-pore domain potassium channel family. They are potently inhibited by local anaesthetics and have been implicated as having important roles in many pathophysiological conditions such as heart arrythmias, stroke, epilepsy, breast and other cancers. The in depth structural and functional characterisation of this class of potassium channels is of great importance as they are interesting targets for new therapeutic developments. Advancement of knowledge in the structure and function of these channels will underpin drug targeting that will aid preventative healthcare, allowing Australians to age well and age productively.Read moreRead less
Metal-Based Anti-inflammatory Drugs with High Efficacy and Low Side-Effects. Non-steroidal anti-inflammatory drugs (NSAIDs) have widespread human and veterinary applications for the treatment of arthritis and other inflammatory diseases, but their utility is limited by often severe gastrointestinal, renal and cardiac side-effects. The recently heralded COX-2 inhibitors have not lived up to their expectations in terms of efficacy and side-effects, therefore, there is a need to develop new potent ....Metal-Based Anti-inflammatory Drugs with High Efficacy and Low Side-Effects. Non-steroidal anti-inflammatory drugs (NSAIDs) have widespread human and veterinary applications for the treatment of arthritis and other inflammatory diseases, but their utility is limited by often severe gastrointestinal, renal and cardiac side-effects. The recently heralded COX-2 inhibitors have not lived up to their expectations in terms of efficacy and side-effects, therefore, there is a need to develop new potent, but safer, NSAIDs. This project is aimed at using the results from new lead compounds to design NSAIDs with much greater efficacy and much less side effects than those currently available.Read moreRead less
Synthesis of Novel Biomaterials for Drug delivery. A new UV radiation polymerisation technique utilising charge-transfer complexes is adopted for synthesising novel hydrogels, a group of biomaterials for drug delivery. This work is significant as charge-transfer complexes, pertinent to the formation of hydrogels, form copolymers within the hydrogel matrices. This eliminates using costly, yet undesirable photo-initiators (PI), thus rendering the hydrogels as cleaner (PI-free) and more economical ....Synthesis of Novel Biomaterials for Drug delivery. A new UV radiation polymerisation technique utilising charge-transfer complexes is adopted for synthesising novel hydrogels, a group of biomaterials for drug delivery. This work is significant as charge-transfer complexes, pertinent to the formation of hydrogels, form copolymers within the hydrogel matrices. This eliminates using costly, yet undesirable photo-initiators (PI), thus rendering the hydrogels as cleaner (PI-free) and more economical in production; the products present themselves as ideal treatment methods in the controlled-release of drugs, specifically targeting localised pathological sites of interest. The research findings will be invaluable to medical practices, leading to the creation of new industries in Australia.
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The Design of New Integrase Inhibitors Targeting HIV-1. There is still no cure in sight for the worldwide HIV pandemic and the worsening viral resistance problem creates a need to find new and novel compounds for therapeutic use. This project aims to design and synthesize new anti-HIV drugs by targeting two separate enzymes within the HIV life-cycle. This 'dual-action' approach of designing a single molecular scaffold to target separate enzymes would enable a synergistic effect while minimizing ....The Design of New Integrase Inhibitors Targeting HIV-1. There is still no cure in sight for the worldwide HIV pandemic and the worsening viral resistance problem creates a need to find new and novel compounds for therapeutic use. This project aims to design and synthesize new anti-HIV drugs by targeting two separate enzymes within the HIV life-cycle. This 'dual-action' approach of designing a single molecular scaffold to target separate enzymes would enable a synergistic effect while minimizing development costs. The expected outcomes from this medicinal chemistry project include the discovery of new compounds with the potential for further development as therapeutic agents against HIV.Read moreRead less
Radiolabelled MMP binding agents for the identification, quantification, and targeting of MMPs in central nervous system (CNS) disorders and tumours. Cancer and diseases of the central nervous system (CNS) represent two of the major health challenges facing Australia because of the aging population. In order to address these challenges we need to develop methods for identifying tumours and CNS diseases using non-invasive technologies and at an early stage so that treatments can be applied when t ....Radiolabelled MMP binding agents for the identification, quantification, and targeting of MMPs in central nervous system (CNS) disorders and tumours. Cancer and diseases of the central nervous system (CNS) represent two of the major health challenges facing Australia because of the aging population. In order to address these challenges we need to develop methods for identifying tumours and CNS diseases using non-invasive technologies and at an early stage so that treatments can be applied when they are most likely to work. In this project, we are developing new radiolabelled compounds that will enable the imaging of tumours, tumour metastases and CNS diseases states.Read moreRead less
The Design and Development of the Next Generation Anti-HIV Drugs. This medicinal chemistry project will develop new computer-aided modelling techniques for drug design and development and will then apply them to the design of new therapeutics for the treatment of HIV-1/AIDS. Once developed, these new techniques can also be applied to other disease targets including various cancers, where specific proteins have been identified as causative. This research will also contribute to the education of y ....The Design and Development of the Next Generation Anti-HIV Drugs. This medicinal chemistry project will develop new computer-aided modelling techniques for drug design and development and will then apply them to the design of new therapeutics for the treatment of HIV-1/AIDS. Once developed, these new techniques can also be applied to other disease targets including various cancers, where specific proteins have been identified as causative. This research will also contribute to the education of young scientists, training them in cutting-edge research skills.Read moreRead less
Oral Insulin Delivery facilitated by Enteric Coating using Dense Gas Technologies. Insulin dependant diabetes is a rapidly growing disease. The current method for insulin delivery to the patient is by injection, which is inconvenient. Oral delivery of insulin is a more acceptable method. It is proposed to develop a dense gas technique to coat insulin with a pH sensitive polymer to protect it from the acidic environment of the stomach. Insulin can then be released at the high pH of the intestin ....Oral Insulin Delivery facilitated by Enteric Coating using Dense Gas Technologies. Insulin dependant diabetes is a rapidly growing disease. The current method for insulin delivery to the patient is by injection, which is inconvenient. Oral delivery of insulin is a more acceptable method. It is proposed to develop a dense gas technique to coat insulin with a pH sensitive polymer to protect it from the acidic environment of the stomach. Insulin can then be released at the high pH of the intestine when the polymer is dissolved. Particle size control is feasible by dense gas processes by manipulating operating parameters. Advantages include low residual solvent and manufacture at ambient temperatures.Read moreRead less
Rational Design of Pegylated Dendrimer Nanostructures for Site Specific Drug Delivery. This project will provide technological advances with significant benefits in terms of improved drug treatment, and therefore health outcomes for Australia. The project builds on areas of research strength in Australia (nanotechnology and biotechnology/biomaterials) and will add considerably to the expanding Australian expertise-base in dendrimer technology (in which it is a world leader). The interdisciplinar ....Rational Design of Pegylated Dendrimer Nanostructures for Site Specific Drug Delivery. This project will provide technological advances with significant benefits in terms of improved drug treatment, and therefore health outcomes for Australia. The project builds on areas of research strength in Australia (nanotechnology and biotechnology/biomaterials) and will add considerably to the expanding Australian expertise-base in dendrimer technology (in which it is a world leader). The interdisciplinary nature of this project will also result in a unique training program for the researchers included in this grant. Such experience is in great demand, particularly in Australia where the burgeoning start-up discovery industry is critically short of personnel with skills in drug delivery.Read moreRead less
Synthetic derivatives of capsaicin and gingerols as analgesics acting at the vanilloid receptor. This project aims to prepare alpha-hydroxyketones and gingerol derivatives acting at vanilloid (VR1) receptor with potential analgesic activity. These compounds will be tested for their ability to activate the VR1 receptor, desensitize the receptor and release neuropeptides associated with pain pathways. The development of these novel compounds will contribute towards understanding the mechanisms of ....Synthetic derivatives of capsaicin and gingerols as analgesics acting at the vanilloid receptor. This project aims to prepare alpha-hydroxyketones and gingerol derivatives acting at vanilloid (VR1) receptor with potential analgesic activity. These compounds will be tested for their ability to activate the VR1 receptor, desensitize the receptor and release neuropeptides associated with pain pathways. The development of these novel compounds will contribute towards understanding the mechanisms of VR1 receptor activation and provide information on how the VR1 receptor is regulated. We will determine and compare neurotoxicity of these compounds to capsaicin which is known to possess neurotoxic activity. The outcome of this project may result in effective agents for better pain management.
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