Reference #: 01658
The University of South Carolina is offering licensing opportunities for therapeutic gossypol-based inhibitors of glucose kinases for parasitic diseases.
Background:
Trypanosoma cruzi and Trypanosoma brucei, which are protozoan parasites pathogenic to the human host are the etiological agents of Chagas' disease and human African trypanosomiasis, respectively. These trypanosomatid parasites individually depend on glycolysis, the pentose phosphate pathway, and gluconeogenesis for their survival. The metabolite D-glucose-6-phosphate (G6P) is at a nodal point between these three pathways. Moreover, glucose kinases (enzymes part of glycolysis) that are responsible in the conversion of D-glucose to G6P are found in T. cruzi as hexokinase and glucokinase, and in T. brucei as hexokinase-1 and hexokinase-2. By inhibiting the glucose kinases in a simultaneous manner (for a given parasite), the flux of G6P production becomes constricted and results in parasite cell death.
Invention Description:
The investigational compounds of this patent were tested against T. cruzi glucokinase, T. cruzi (Tulahuen strain, infective form) co-cultured in mammalian NIH-3T3 fibroblasts, T. brucei brucei bloodstream form, and NIH-3T3 fibroblasts alone. We have discovered compounds exhibiting strong antitrypanosomal activity and lesser host cell toxicity.
Potential Applications:
T. cruzi treatment relies on two main clinically available therapeutic compounds in Latin American countries, such as benznidazole and nifurtimox. These therapeutic drugs have been developed over 55 years ago, alternative options have not emerged, and they present intolerable side effects. New therapeutics have thus been in high demand for a long time. Similarly, T. brucei has various therapeutic drugs that are available for treatment, such as pentamidine, suramin, eflornithine, and melarsoprol. These therapeutics require substantial improvements in their tolerability, safety, and efficacy. A need exists for new compounds that strongly bind to drug targets found in these parasites. Such a need includes inhibitors of the trypanosomatid glucose kinases. The investigational compounds (inhibitors) covered in this patent are to provide alternatives to the current clinically used therapeutic drugs.
Advantages and Benefits:
These are newly identified inhibitors of trypanosomatid glucose kinases, which can also be used against other pathogenic organisms. The investigational compounds proposed in this patent may serve as viable substitutes for the currently used therapeutic drugs in the clinic.