Neglected tropical diseases (NTDs) are a group of parasitic diseases that disproportionately affect those living in poverty. Consequently, there is little economic incentive to develop new drugs that meet needs related to efficacy and safety. To address this, our lab focuses on repurposing both early and late-stage chemical matter as inhibitors of parasite proliferation, and then performing hit-to-lead medicinal chemistry optimization to fine-tune these hits.
One of the diseases for which we have employed this strategy is human African trypanosomiasis (HAT), an NTD that affects approximately 8,000 people in the most remote parts of Africa. It is devastating to those afflicted and the treatments that are available are not 100% effective and can cause severe side effects, and thus new drugs are needed. Throughout our optimization efforts we have engaged with collaborators across multiple disciplines to further the progression of several compounds to preclinical evaluation. This highly collaborative approach has enabled us to expand our program to include optimization against Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum, among others. This presentation will highlight the distributed drug discovery paradigm we have employed in the hit-to-lead optimization of compounds against multiple disease-causing pathogens, and describe the results of this optimization.