Targeting DNA with Dynamic Combinatorial Chemistry. The interaction of molecules with DNA, the molecule that controls genetic information, is fundamental to drug design, diagnosis of disease and the environment. Chemists usually synthesise these molecules in the laboratory. We will use an innovative new approach to producing molecules that interact with DNA, that as fast and efficient and mirrors the processes used by Nature to make natural products. This research may lead to the design of new ....Targeting DNA with Dynamic Combinatorial Chemistry. The interaction of molecules with DNA, the molecule that controls genetic information, is fundamental to drug design, diagnosis of disease and the environment. Chemists usually synthesise these molecules in the laboratory. We will use an innovative new approach to producing molecules that interact with DNA, that as fast and efficient and mirrors the processes used by Nature to make natural products. This research may lead to the design of new therapeutics, diagnostics and applications that will benefit the Australian community, and will provide excellent training of researchers in skills required for employment in the biotechnology and pharmaceutical fields.Read moreRead less
Platinum-Carborane Complexes as New Agents for Boron Neutron Capture Therapy. The development of new drugs and treatments for cancer is highly important to human health and the well-being of the community. This research has the potential to lead to new anticancer pharmaceuticals that will expand the clinical efficacy of current drugs and generate significant export income through future IP development and possible commercialization. The innovative nature of this research will also contribute t ....Platinum-Carborane Complexes as New Agents for Boron Neutron Capture Therapy. The development of new drugs and treatments for cancer is highly important to human health and the well-being of the community. This research has the potential to lead to new anticancer pharmaceuticals that will expand the clinical efficacy of current drugs and generate significant export income through future IP development and possible commercialization. The innovative nature of this research will also contribute to Australia's science knowledge base, a key element in its future economic prosperity, and it will provide excellent training of young researchers for employment in the rapidly expanding field of biotechnology.Read moreRead less
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
Encapsulation of magnetic nanoparticles for the hyperthermia treatment of liver cancer. This project will provide targeted hyperthermia treatment for liver cancer. The treatment will be non systemic and therefore, unlike radiotherapy and chemotherapy, will cause minimal collateral damage to healthy tissue within the patient. Liver cancer is one of the commoner forms of cancer in humans with estimates of up to 2 million patients per year being affected worldwide. Currently 95% of these patients w ....Encapsulation of magnetic nanoparticles for the hyperthermia treatment of liver cancer. This project will provide targeted hyperthermia treatment for liver cancer. The treatment will be non systemic and therefore, unlike radiotherapy and chemotherapy, will cause minimal collateral damage to healthy tissue within the patient. Liver cancer is one of the commoner forms of cancer in humans with estimates of up to 2 million patients per year being affected worldwide. Currently 95% of these patients will die from the condition. This project will lead to improvements in health outcomes for liver cancer patients. As a consequence of the worldwide demand for this treatment, and related equipment, the project will generate foreign exchange earnings through exports and new job opportunities in the clever end of small business enterprise.Read moreRead less
Multivalent drug delivery carrier for the targeted delivery of platinum anticancer agents to hepatocytes. Hepatocellular carcinoma (HCC) is often treated with chemotherapy using cytotoxic drugs. This systemic treatment results in the distribution of the drug throughout the body. Employing a polymer particle as a drug carrier for these drugs ensures a temporal control of the release and therefore supply of the drug within the body. By attaching carbohydrate moieties onto the surface of the polyme ....Multivalent drug delivery carrier for the targeted delivery of platinum anticancer agents to hepatocytes. Hepatocellular carcinoma (HCC) is often treated with chemotherapy using cytotoxic drugs. This systemic treatment results in the distribution of the drug throughout the body. Employing a polymer particle as a drug carrier for these drugs ensures a temporal control of the release and therefore supply of the drug within the body. By attaching carbohydrate moieties onto the surface of the polymer particle the drug carrier can specifically be recognized by cell receptors, thus allowing a targeted delivery of the drug to the desired area in the body. A range of carbohydrate-based drug carriers will be synthesized and tested towards their interaction with hepatocytes to allow optimisation of this drug carrier system.
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New Strategies for Monitoring DNA-Anticancer Drug Interactions. The highly successful cisplatin works by binding to DNA and partially unwinding or bending the DNA. As a consequence of the success if cisplatin, alternative anticancer drugs are being developed with reduced side effects for patients. One of the bottom necks in the development of alternative drugs is rapid screening of the efficacy on new leads. The proposed research will develop new technologies for monitoring DNA-drug binding, ....New Strategies for Monitoring DNA-Anticancer Drug Interactions. The highly successful cisplatin works by binding to DNA and partially unwinding or bending the DNA. As a consequence of the success if cisplatin, alternative anticancer drugs are being developed with reduced side effects for patients. One of the bottom necks in the development of alternative drugs is rapid screening of the efficacy on new leads. The proposed research will develop new technologies for monitoring DNA-drug binding, DNA damage and DNA repair using novel DNA biosensors. the novelty of the biosensor technology will be to use the modulation of charge transfer through DNA as a method for determining the structural changes that occur in DNA due to these events occurring.Read moreRead less
Synthesis of the pyrrolo[2,1-c][1,4]benzodiazepines: potent DNA binders. Chemicals that bind to DNA have a long history of use as anticancer drugs. In recent times, the biotechnology revolution has greatly expanded our understanding of how these drugs work and the genetic basis of a wide range of other diseases. The aim of this project is to discover novel compounds that selectively bind to DNA. Starting from a class of naturally occurring compounds (called the pyrrolobenzodiazepines) as a templ ....Synthesis of the pyrrolo[2,1-c][1,4]benzodiazepines: potent DNA binders. Chemicals that bind to DNA have a long history of use as anticancer drugs. In recent times, the biotechnology revolution has greatly expanded our understanding of how these drugs work and the genetic basis of a wide range of other diseases. The aim of this project is to discover novel compounds that selectively bind to DNA. Starting from a class of naturally occurring compounds (called the pyrrolobenzodiazepines) as a template, it will develop powerful new methods to supply wholly new DNA interactive molecules with great potential as new drugs to treat cancer or other genetic diseases.Read moreRead less
Anti-Cancer Natural Products: Total Synthesis and Biological Evaluation of Lasonolide A and Analogues. One in three men and one in four women in Australia will be diagnosed with cancer before they reach 75. Cancer is a leading cause of death within this country with 28% of deaths each year due to this disease. Although there have been advances in the treatment of various forms of cancer there remains a pressing need for new therapies with improved potency, selectivity and reduced side effects. T ....Anti-Cancer Natural Products: Total Synthesis and Biological Evaluation of Lasonolide A and Analogues. One in three men and one in four women in Australia will be diagnosed with cancer before they reach 75. Cancer is a leading cause of death within this country with 28% of deaths each year due to this disease. Although there have been advances in the treatment of various forms of cancer there remains a pressing need for new therapies with improved potency, selectivity and reduced side effects. This project will provide new compounds of potential clinical use in the treatment of cancer, thereby aiding the large population of Australians who will be affected by this disease. Furthermore, the new advanced materials produced by this project will aid in the study of biochemical processes involved in cancer.Read moreRead less
High Pressure and Fluorous Approaches to Fostriecin Libraries: New Therapeutic Opportunities. The natural product, Fostriecin, displays considerable broad-spectrum anti-cancer activity, acting via a novel mechanism. However, this activity is tempered by its considerable instability, being too unstable to be used as a therapeutic agent. Using state-of-the-art approaches we will, rapidly generate libraries of more stable and biologically active fostriecin analogues and examine their potential to b ....High Pressure and Fluorous Approaches to Fostriecin Libraries: New Therapeutic Opportunities. The natural product, Fostriecin, displays considerable broad-spectrum anti-cancer activity, acting via a novel mechanism. However, this activity is tempered by its considerable instability, being too unstable to be used as a therapeutic agent. Using state-of-the-art approaches we will, rapidly generate libraries of more stable and biologically active fostriecin analogues and examine their potential to be used anti-cancer agents. This project represents an opportunity for Australia to take a significant, innovative lead in the development of hitherto unforseen therapeutic agents.Read moreRead less
Redox-Tuneable Sensitisers for Photodynamic Therapy of Malignant and Non-Malignant Proliferative Diseases. Cancer is currently Australia's leading cause of death with 85 231 new cases reported during 2000, costing the health system >$2 billion annually. Photodynamic Therapy is a promising anti-cancer therapy which combines the action of a photosensitising drug and light to destroy tumours. This project will lead to the development of new photosensitisers which will enable the specific targeting ....Redox-Tuneable Sensitisers for Photodynamic Therapy of Malignant and Non-Malignant Proliferative Diseases. Cancer is currently Australia's leading cause of death with 85 231 new cases reported during 2000, costing the health system >$2 billion annually. Photodynamic Therapy is a promising anti-cancer therapy which combines the action of a photosensitising drug and light to destroy tumours. This project will lead to the development of new photosensitisers which will enable the specific targeting of tumours while protecting healthy tissue from damage. Post-treatment skin photosensitivity will be minimised by antioxidant features integrated into the photosensitisers. The development of improved photosensitisers during this project will ultimately lead to improved treatment and new alternatives for Australian cancer sufferers.Read moreRead less