Description:
Reference #: 01133
The University of South Carolina is offering licensing opportunities for new enzyme inhibitors for therapeutic drugs that treat diseases caused by trypanosomal parasites including Chagas’ disease and African sleeping sickness.
Invention Description:
Trypanosomal parasites, such as Trypansoma cruzi and Trypansoma brucei, utilize glycolysis, which is an essential energy-producing metabolic pathway. Since glycolysis is indispensable for these organisms, obstruction of the pathway leads to cell death. This obstruction can be achieved by inhibiting the hexokinase and glucokinase enzymes using drug compounds.
Specifically, the subject invention describes experimentally confirmed selective inhibitors of T. cruzi glucokinase. These compounds are useful as therapeutic drugs because they selectively inhibit the parasite homologue and avoid cross-reactivity with the human homologue Homo sapiens glucokinase, giving rise to a good selectively ratio.
Potential Applications:
These compounds offer an alternative to commonly prescribed drugs for two diseases of the trypanosome, including American Trypanosomiasis (Chagas' Disease), which is caused by the T. cruzi parasite, and African Trypanosomiasis (African Sleeping Sickness), which is caused by the T. brucei parasite.
Advantages and Benefits:
This is a new type of drug that can be used against certain validated drug-targets (glucokinase and hexokinase) that are found in protozoan parasites. These compounds may serve as viable substitutes for currently used drugs in clinics, pending in vitro studies.
Background:
Chagas’ disease has two standard-of-care treatments available: benznidazole and nifurtimox, which were developed over 35 years ago. African sleeping sickness has been reliant on a variety of drugs, such as pentamidine, suramin, eflornithine, and melarsoprol; however, all current medicines for both diseases require substantial improvements in their tolerability, safety, and efficacy.
Experimental Validation:
The proposed drug compounds show confirmed strong selective inhibition for the drug-target T. cruzi glucokinase compared to the human homologue, Homo sapiens glucokinase. Similar results are expected for T. cruzi hexokinase. Further testing is required on in vitro parasite survival studies and mouse infectivity studies.