Development of small molecule primary sulfonamides as new drugs for malaria. Malaria is a major global health threat, causing approximately 800,000 deaths annually. Lives can be saved if patients are treated. The use of current antimalarial drugs is limited by drug resistance, low activity and poor safety. This project investigates the effectiveness of a new class of molecule as a safe drug treatment option to kill malaria parasites.
Optimisation Of A Potent And Fast Acting Antimalarial Class That Is Orally Efficacious In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$683,916.00
Summary
Malaria is a devastating disease that results in 600 000 deaths annually. Current therapeutics used to combat malaria have a limited duration of use in the clinic due to the onset of resistance. We have identified a highly active antimalarial series that we propose to further develop to meet the prerequisites required for partnership with the Medicines for Malaria Venture (MMV) for progression into the clinic.
Chemical Biology Investigation Of Cell Death Processes: Development Of Molecular Probes Interfering With Necroptosis
Funder
National Health and Medical Research Council
Funding Amount
$630,736.00
Summary
Necroptotic programmed cell death has a key role in maintaining healthy tissue, and dysregulation of this process is associated with the pathology of infection and a range of chronic inflammation diseases for which there are few satisfactory treatments. In this project, we will discover small, drug like, molecules that interfere with the necroptosis pathway. These small molecules have the potential to become new therapeutics to treat these inflammatory diseases and will be invaluable probes to s ....Necroptotic programmed cell death has a key role in maintaining healthy tissue, and dysregulation of this process is associated with the pathology of infection and a range of chronic inflammation diseases for which there are few satisfactory treatments. In this project, we will discover small, drug like, molecules that interfere with the necroptosis pathway. These small molecules have the potential to become new therapeutics to treat these inflammatory diseases and will be invaluable probes to study this key biological pathway.Read moreRead less
Rational design of new drug candidates for the treatment of Trypanosoma cruzi infection. There is a serious shortage of safe and effective drugs to treat Chagas disease which is caused by a parasitic infection. This project aims to design and identify new drug candidates by defining the disposition profile within the body which is necessary to achieve a therapeutic effect.
Translating pharmacokinetic and pharmacodynamic data to better design new drugs for the treatment of Trypanosoma cruzi infection. New drugs to treat T. cruzi infection are urgently needed, however their design has been hampered by an incomplete understanding of complex host-parasite interactions, inadequate in vitro and in vivo tools to rigorously define activity during drug discovery, and a poor appreciation of concentration/effect relationships. This project aims to develop new and much needed ....Translating pharmacokinetic and pharmacodynamic data to better design new drugs for the treatment of Trypanosoma cruzi infection. New drugs to treat T. cruzi infection are urgently needed, however their design has been hampered by an incomplete understanding of complex host-parasite interactions, inadequate in vitro and in vivo tools to rigorously define activity during drug discovery, and a poor appreciation of concentration/effect relationships. This project aims to develop new and much needed in vitro methods to better define the kinetic and dynamic activity of new drug candidates, and will provide a rational basis for translating this information into lengthy animal models of T. cruzi infection. The outcome aims to be rationally designed drug candidates that are available in a shorter period of time and are suitable for further development.Read moreRead less
Capturing New Drugs That Selectively Modulate PAR2 Signaling Pathways
Funder
National Health and Medical Research Council
Funding Amount
$469,088.00
Summary
Infection and tissue damage provoke acute inflammatory responses that sometimes continue unchecked, leading to different kinds of debilitating inflammatory diseases and cancers. We have discovered a new class of drugs that bind to a new target on human cells and block undesirable prolonged inflammatory responses. This project tests a new strategy to produce 'cleaner' drugs that act more selectively with fewer side effects against a new target in the treatment of arthritis and other inflammatory ....Infection and tissue damage provoke acute inflammatory responses that sometimes continue unchecked, leading to different kinds of debilitating inflammatory diseases and cancers. We have discovered a new class of drugs that bind to a new target on human cells and block undesirable prolonged inflammatory responses. This project tests a new strategy to produce 'cleaner' drugs that act more selectively with fewer side effects against a new target in the treatment of arthritis and other inflammatory diseases, diet-induced obesity and cancers.Read moreRead less
Dissecting catalysis and inhibition of a unique endo-acting mannose-processing glycosidase. Defects in the attachment of carbohydrates to proteins are a hallmark of diseases such as cancer and viral infection. This project will dissect the molecular details of the bond-making and breaking steps that occur during the synthesis of glycoproteins assisting in the development of innovative new drugs.
Novel antimicrobial surface coatings for Cochlear implants. The objective of this project is to develop new antimicrobial coatings for materials used to manufacture biomedical devices. Infection associated with the use of biomaterials such as biomedical implants, catheters and orthopaedic prostheses is a major barrier to the use of these devices. The coatings that the project plans to develop are based on novel antimicrobials which have been shown to prevent adhesion and colonisation of biomater ....Novel antimicrobial surface coatings for Cochlear implants. The objective of this project is to develop new antimicrobial coatings for materials used to manufacture biomedical devices. Infection associated with the use of biomaterials such as biomedical implants, catheters and orthopaedic prostheses is a major barrier to the use of these devices. The coatings that the project plans to develop are based on novel antimicrobials which have been shown to prevent adhesion and colonisation of biomaterials by bacteria in vivo. This strategy has the potential to prevent device-related infections and revolutionise the biomaterials industry.Read moreRead less
Screening platforms for malaria drug discovery: identification of new therapeutics. Innovative image based technologies will be developed to identify molecules which stop malaria parasite growth and its transmission to the mosquito host. As more resistance is emerging against the current drugs of choice, new molecules acting through different mechanisms are urgently needed.
Fragment based screening to deliver drugs targeting tuberculosis and the gametocyte and liver stages of Plasmodium. This project will identify natural products that bind to critical proteins in malaria and tuberculosis to discover new ways to treat these diseases.