Inhibitors Of Hypoxanthine-guanine-xanthine Phosphoribosyltransferase As Versatile Drugs To Treat Infectious Diseases
Funder
National Health and Medical Research Council
Funding Amount
$766,163.00
Summary
Due to the increase in resistance to many of the frontline drugs to treat bacterial and parasitic infections, there is an urgent need to develop new pipelines for drug discovery against the pathogens that are causative agents of this diseases. This project pioneers the blocking of nucleotide synthesis to develop new drug leads to treat malaria, human tuberculosis, African sleeping sickness, Chagas disease and uropathogenic E.coli infections.
Targeting Acetohydroxyacid Synthase To Discover New Antifungal Agents.
Funder
National Health and Medical Research Council
Funding Amount
$481,135.00
Summary
Invasive fungal infections are increasingly being recognized as a major life threatening risk to hospitalized patients. The efficacy of the current medications is sub-optimal due to the emergence of resistance and the high dosage regimes that are required to treat these infections. We propose to develop a new class of antifungal agent that target an enzyme, acetohydroxyacid synthase, whose activity is required for the survival of pathogenic fungi in mammals.
Virtual Screening In Structure-Based Drug Design For Malaria
Funder
National Health and Medical Research Council
Funding Amount
$285,000.00
Summary
Malaria continues to be one of the most serious health problems in the world today with approximately 300 million people affected and 1.5 million recorded deaths per year. The most deadly and widespread parasite responsible for this disease is Plasmodium falciparum. Because of the parasite's increasing resistance to traditional medication, there is an urgent need to develop more effective treatments. Two approaches are feasible: vaccines and new drugs. Both will probably be necessary to combat t ....Malaria continues to be one of the most serious health problems in the world today with approximately 300 million people affected and 1.5 million recorded deaths per year. The most deadly and widespread parasite responsible for this disease is Plasmodium falciparum. Because of the parasite's increasing resistance to traditional medication, there is an urgent need to develop more effective treatments. Two approaches are feasible: vaccines and new drugs. Both will probably be necessary to combat the spread and consequences of malaria. We are approaching this problem by targeting an enzyme which is essential for the survival of the parasite. All protozoan parasites make their purine nucleotides (the building blocks of DNA and RNA) by purine base salvage. Unlike humans, they cannot make purines from simple precursor molecules. The key enzyme in the salvage pathway is hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT). Our plan is to capitalize on knowledge of the precise structure of HGXPRT and the increased power of computers to determine which chemicals are able to bind tightly and specifically to the active site of the enzyme. We will then test the ability of these compounds to inhibit purified human and Plasmodium enzymes and their ability to inhibit the growth of the malarial parasite in red cells. Chemical synthesis will be used to improve the effectiveness of these compounds.Read moreRead less