Project Title: Structure-based design of dual inhibitors of trypanosomes glycerol kinase and alternative oxidase for drug development against African trypanosomiasis
Host Organisation: Ahmadu Bello University, Nigeria
This project aims contribute towards the development of new drug for the treatment of two major diseases that have been partly attributed to the poverty and underdevelopment of Africa. The diseases are sleeping sickness and nagana, affecting humans and livestock, respectively and they are caused by parasites known as African trypanosomes. Thousands of African people are killed annually by sleeping sickness and an estimated annual loss of up to 5 billion US dollars resulting from millions of cattle, camels, and small ruminants being killed by nagana. Very few drugs are available for treatment and they are faced with problems such as treatment failures, high toxicities, and narrow spectrum (drugs for treating animals cannot be used to treat humans). We have studied the energy production pathway of the parasites and identified that the parasites are effectively killed when two key enzymes of the pathway, trypanosome glycerol kinase (TGK) and trypanosome alternative oxidase (TAO) are simultaneously blocked. We have studied these enzymes in detail. Our data revealed that it is feasible to obtain chemical compounds that can inhibit the enzymes and not elicit deleterious side effects in humans and animals during treatment. The novelty in this proposal is that I will design a single compound that will block both TGK and TAO simultaneously. If successful, the compounds will be helpful in the formulation of new drug(s) to treat both humans and animals in Africa and contribute towards increased quality of life and prosperity of the African people.