Discovery Of New And Better Treatments For Human African Trypanosomiasis
Funder
National Health and Medical Research Council
Funding Amount
$837,615.00
Summary
Sleeping sickness, or human African trypanosomiasis, is present in 36 countries where there are 60 million people at risk of infection, with 50,000-70,000 new cases and 48,000 deaths per annum. Transmitted by the bite of the tsetse fly, this disease is caused by the protozoan parasite Trypanosoma brucei, and without treatment, death is inevitable. We have discovered some compounds that weakly inhibit T.brucei and the aim of this project is to make them potent enough to become drug candidates.
The effect of Pt binding to CTR1 on Cu homeostasis and cell phenotype. The copper transport protein CTR1 is commonly believed to transport active cisplatin (a platinum-based anticancer agent) into the cell, but this model is inconsistent with the chemical properties of platinum (Pt) and CTR1. The project aims to interrogate the interaction between CTR1 and Pt in cells by developing new chemical tools for the study of Pt species within cells. It will then study the effect of the CTR1-Pt interacti ....The effect of Pt binding to CTR1 on Cu homeostasis and cell phenotype. The copper transport protein CTR1 is commonly believed to transport active cisplatin (a platinum-based anticancer agent) into the cell, but this model is inconsistent with the chemical properties of platinum (Pt) and CTR1. The project aims to interrogate the interaction between CTR1 and Pt in cells by developing new chemical tools for the study of Pt species within cells. It will then study the effect of the CTR1-Pt interaction on copper homeostasis and cell phenotype. It is expected that the results will provide valuable information on the status of CTR1 and Pt following interaction, and reveal whether less toxic complexes are just as effective in decreasing cell malignancy as cisplatin itself.Read moreRead less
Novel platinum(IV) complexes that are targeted to and trapped by tumours and tumour cells. Platinum complexes continue to be a mainstay in the treatment of solid tumours and their combination with molecularly targeted agents selected for the type of tumour and the mutations identified is expected to lead to continued growth in their use. However, their toxicity remains a major impediment to their use and effectiveness and therefore, this project aims to develop less toxic analogues that are as l ....Novel platinum(IV) complexes that are targeted to and trapped by tumours and tumour cells. Platinum complexes continue to be a mainstay in the treatment of solid tumours and their combination with molecularly targeted agents selected for the type of tumour and the mutations identified is expected to lead to continued growth in their use. However, their toxicity remains a major impediment to their use and effectiveness and therefore, this project aims to develop less toxic analogues that are as least as effective as current drugs. This project will combine recent developments in stabilisation and cellular trapping of platinum(IV) pro-drugs with a range of strategies designed to limit activation of these pro-drugs to the tumour environment.Read moreRead less