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Towards Next Generation Anthelmintics. The agricultural industry is in urgent need of new, safe and cost effective treatments for parasite infections in commercial livestock (sheep, cattle, goats). The current multi billion dollar agrochemical industry provides only three classes of antiparasitic drug, all of which are >25 yrs old and are largely ineffective due to the widespread resistance. This project will advance the development of a new class of antiparasitic treatment, improving outcomes f ....Towards Next Generation Anthelmintics. The agricultural industry is in urgent need of new, safe and cost effective treatments for parasite infections in commercial livestock (sheep, cattle, goats). The current multi billion dollar agrochemical industry provides only three classes of antiparasitic drug, all of which are >25 yrs old and are largely ineffective due to the widespread resistance. This project will advance the development of a new class of antiparasitic treatment, improving outcomes for Australian farmers by reducing reliance on expensive ineffective agrochemical imports, reducing chemical load on the environment, improving pastures and increasing yields. In short, improved livestock health will lead to more sustainable and productive farming, and a stronger economy.Read moreRead less
Development and Biological Chemistry of Novel Platinum Anti-Cancer Agents. "Rule-breakers", platinum anticancer complexes that do not follow the well established structure/activity relationships, have emerged as the way forward in the treatment of cancer resistant to the current generation of drugs and in reducing side effects. We have developed two new groups of "rule-breakers" and these have already demonstrated highly promising anticancer activity and novel biological behaviour. In this proje ....Development and Biological Chemistry of Novel Platinum Anti-Cancer Agents. "Rule-breakers", platinum anticancer complexes that do not follow the well established structure/activity relationships, have emerged as the way forward in the treatment of cancer resistant to the current generation of drugs and in reducing side effects. We have developed two new groups of "rule-breakers" and these have already demonstrated highly promising anticancer activity and novel biological behaviour. In this project we will (i) prepare new anticancer active platinum complexes based on these two highly promising groups of compounds and (ii) determine how these drugs work and what happens to them when in biological environments.Read moreRead less
NMR Studies of Second Generation Polynuclear Platinum Compounds. Cancer affects one in four Australians and 50% of cancer patients are treated with cisplatin. BBR3464 is a new type of platinum anticancer drug that has shown promise in clinical trials, including results in cancers that do not respond to cisplatin treatment. Second-generation analogues, now under development, may offer significant advantages. This international collaboration between Prof. Berners-Price and the inventor of these ne ....NMR Studies of Second Generation Polynuclear Platinum Compounds. Cancer affects one in four Australians and 50% of cancer patients are treated with cisplatin. BBR3464 is a new type of platinum anticancer drug that has shown promise in clinical trials, including results in cancers that do not respond to cisplatin treatment. Second-generation analogues, now under development, may offer significant advantages. This international collaboration between Prof. Berners-Price and the inventor of these new drugs puts Australian research at the forefront of the clinical development. There is the potential for the generation of new IP from new strategies in the design of improved anticancer drugs. The project builds strong international links and provides international training for Australian PhD students.Read moreRead less
DNA interactions of polynuclear platinum. Mechanistic NMR studies probing the origin of the unique antitumour activity of BBR3464. BBR3464 is one of a class of structurally unique platinum anticancer drugs that is currently undergoing clinical trials. The anticancer activity most likely depends on binding to DNA, but the mechanism is quite different from that of the widely used drug, cisplatin. This project uses NMR spectroscopy to follow the processes involved in the initial binding of the dr ....DNA interactions of polynuclear platinum. Mechanistic NMR studies probing the origin of the unique antitumour activity of BBR3464. BBR3464 is one of a class of structurally unique platinum anticancer drugs that is currently undergoing clinical trials. The anticancer activity most likely depends on binding to DNA, but the mechanism is quite different from that of the widely used drug, cisplatin. This project uses NMR spectroscopy to follow the processes involved in the initial binding of the drug to DNA and the subsequent reactions of the adducts formed. The results of this work will aid in the selection of back-up clinical candidates and in the design of drugs that target specific sequences of DNA for use in novel gene-based therapies.Read moreRead less
Probing polynuclear platinum biomolecule interactions. Cancer affects one in four Australians and 50% of cancer patients are treated with cisplatin. BBR3464 is a new type of platinum anticancer drug that has shown promise in clinical trials, including results in cancers that do not respond to cisplatin treatment. Second-generation analogues, now under development, may offer significant advantages. This international collaboration with the inventor of these new drugs puts Australian research at t ....Probing polynuclear platinum biomolecule interactions. Cancer affects one in four Australians and 50% of cancer patients are treated with cisplatin. BBR3464 is a new type of platinum anticancer drug that has shown promise in clinical trials, including results in cancers that do not respond to cisplatin treatment. Second-generation analogues, now under development, may offer significant advantages. This international collaboration with the inventor of these new drugs puts Australian research at the forefront of the clinical development. There is the potential for the generation of new IP from new strategies in the design of improved anticancer drugs. The project builds strong international links and provides international training for Australian PhD students. Read moreRead less
Design, Evaluation, and Selection of Novel Pt(IV) Complexes as Anticancer Agents. Platinum anticancer drugs are arguably the most widely used anticancer agents in the world but serious problems remain with toxicity and resistance. Platinum(IV) compounds have numerous advantages in terms of stability and thereby, lower toxicity. In this project we will exploit these advantages along with others that we have discovered recently and our understanding of the chemistry and biology of platinum(IV) to ....Design, Evaluation, and Selection of Novel Pt(IV) Complexes as Anticancer Agents. Platinum anticancer drugs are arguably the most widely used anticancer agents in the world but serious problems remain with toxicity and resistance. Platinum(IV) compounds have numerous advantages in terms of stability and thereby, lower toxicity. In this project we will exploit these advantages along with others that we have discovered recently and our understanding of the chemistry and biology of platinum(IV) to develop novel platinum(IV) compounds to the point where the industry partner can commercialise them.Read moreRead less
Second Generation Polynuclear Platinum Compounds. Mechanistic NMR Studies Probing DNA Binding and Pharmacokinetics. Cancer affects one in four Australians and 50% of cancer patients are treated with cisplatin. BBR3464 is a new type of platinum anticancer drug that has shown promise in clinical trials, including results in cancers that do not respond to cisplatin treatment. Second-generation analogues, now under development, may offer significant advantages. This international collaboration betwe ....Second Generation Polynuclear Platinum Compounds. Mechanistic NMR Studies Probing DNA Binding and Pharmacokinetics. Cancer affects one in four Australians and 50% of cancer patients are treated with cisplatin. BBR3464 is a new type of platinum anticancer drug that has shown promise in clinical trials, including results in cancers that do not respond to cisplatin treatment. Second-generation analogues, now under development, may offer significant advantages. This international collaboration between Prof. Berners-Price and the inventor of these new drugs puts Australian research at the forefront of the clinical development. There is the potential for the generation of new IP from new strategies in the design of improved anticancer drugs. The project builds strong international links and provides international training for Australian PhD students. Read moreRead less
NMR studies on DNA interactions of polynuclear platinum. BBR3464 is representative of a class of structurally unique platinum anticancer drugs, and is currently undergoing clinical trials. The anticancer activity most likely depends on binding to DNA, but the mechanism is different from that of the widely used drug, cisplatin. This project uses NMR spectroscopy to follow in detail the stepwise formation of DNA adducts. Further extension to reactions of polynuclear platinum complexes with sulfur ....NMR studies on DNA interactions of polynuclear platinum. BBR3464 is representative of a class of structurally unique platinum anticancer drugs, and is currently undergoing clinical trials. The anticancer activity most likely depends on binding to DNA, but the mechanism is different from that of the widely used drug, cisplatin. This project uses NMR spectroscopy to follow in detail the stepwise formation of DNA adducts. Further extension to reactions of polynuclear platinum complexes with sulfur nucleophiles will aid in understanding their metabolism and toxicity. The results of this work will aid in the selection of back-up clinical candidates and the design of drugs that target specific sequences of DNA for use in novel gene-based therapies.Read moreRead less
Gold phosphine and carbene complexes as potential antimitochondrial anticancer agents: design, synthesis and biological chemistry. To overcome the two major problems associated with existing anticancer drugs (resistance to therapy and lack of discrimination between normal and cancer cells) there is much current interest in targeting mitochondrial cell death pathways in chemotherapy. This project will probe the mode of action of a series of gold complexes containing pyridylphosphines that may ac ....Gold phosphine and carbene complexes as potential antimitochondrial anticancer agents: design, synthesis and biological chemistry. To overcome the two major problems associated with existing anticancer drugs (resistance to therapy and lack of discrimination between normal and cancer cells) there is much current interest in targeting mitochondrial cell death pathways in chemotherapy. This project will probe the mode of action of a series of gold complexes containing pyridylphosphines that may act by an antimitochondrial mechanism. Also, we will evaluate a new family of gold complexes based on carbene rather than phosphine components. Such compounds offer the potential advantages of ease of synthesis, lower toxicity and the ability to fine-tune molecular properties to maximise anticancer activity.Read moreRead less
Chemical and Biochemical Characterisation of Novel Iron Chelators with Therapeutic Potential. Resistance by cancers to established chemotherapeutics is a growing problem in the community and one that demands the development of new strategies. Chelators that target the essential element iron within cancer cells represent a novel and promising approach to this problem. The Chief Investigators represent a unique combination of expertise in coordination chemistry and the biochemistry of iron chelati ....Chemical and Biochemical Characterisation of Novel Iron Chelators with Therapeutic Potential. Resistance by cancers to established chemotherapeutics is a growing problem in the community and one that demands the development of new strategies. Chelators that target the essential element iron within cancer cells represent a novel and promising approach to this problem. The Chief Investigators represent a unique combination of expertise in coordination chemistry and the biochemistry of iron chelation. They have discovered and characterised new chelators that show marked anticancer activity, and act by a new mechanism that overcomes problems of resistance. In this project they will pursue a course that will lead to a greater understanding of how these compounds work with the outcome that new effective anticancer drugs may emerge.Read moreRead less