Inhibitors of Glucose Kinases

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Background: Human pathogenic, protozoan parasites of the trypanosome, which include Trypanosoma cruzi, T. brucei, and Leishmania spp. contribute to the Neglected Tropical Diseases (NTDs) of the world.  Available chemotherapeutics for these diseases by healthcare professionals require substantial improvements to their safety, tolerability, and efficacy.  There is also a growing concern about drug resistance as well.  A need exists for new drugs that strongly bind to drug targets found in these parasites. Such a need includes inhibitors of the glucose kinase enzymes, such as hexokinase and glucokinase. The inhibitors covered by this technology provide alternatives to clinically used drugs. Invention Description: The compounds for this patent are experimentally-confirmed strong inhibitors of T. cruzi glucose kinases. The compounds impede essential biochemical pathways that lead to parasite cell death. This is achieved by inhibition (using an inhibitor/drug) of the glucose kinase enzymes. Potential Applications: The subject invention –compounds– are strong inhibitors of kinetoplastid parasites, such as T. cruzi, T. brucei, and Leishmania spp., and would therefore be promising next-step candidates for the treatment of Chagas’ Disease, African Sleeping Sickness, and Leishmaniasis to replace the existent drugs. T. cruzi is the causative agent for Chagas’ Disease and available therapeutics include benznidazole and nifurtimox that were in the market for over 30 years.  T. brucei is the causative agent for human African Sleeping Sickness, for which various drugs are available such as pentamidine, suramin, eflornithine, and melarsoprol.  Leishmania protozoa cause Leishmaniasis and available treatments include amphotericin B deoxycholate, pentamidine isethionate, and the orally administered azole-based drugs (ketoconazole, itraconazole, and fluconazole). Advantages and Benefits: The subject invention consists of newly identified strong inhibitors of glucose kinases, which are found in protozoan parasites and other pathogenic organisms. The proposed compounds serve as promising candidate leads for the replacement of the currently used NTD drugs in the market and in vitro parasite studies as well as mouse infectivity studies are in progress.  The goal is that these compounds will serve to be more efficacious and less toxic. Development: The solid oxide fuel cell devices have been fabricated based this invention and the performance of the device has been successfully measured.