Session: Posters:

Human African Trypanosomiasis (HAT) is a neglected tropical disease caused by the protozoan Trypanosoma brucei, that is transmitted by infected tsetse flies. HAT is endemic in 36 sub-Saharan African countries. A sustained effort to find new orally- available drug leads is crucial to containment of the disease in the long-term, since resistance is expected for drugs in use or approved. To that end, a set of new carbazole derivatives was tested for anti-trypanosome activity, following up on our work with NEU-5161 (CBL0137) that prevented division of the cell nucleus. NEU-5161 is orally bioavailable, and in a mouse model of the disease it cured acute HAT.Progress towards advancing the development of carbazole hits, including structure-activity relationships (SAR), and structure property relationships (SPR), leading to identification of a potent lead compound with improved ADME properties will be reported.

Michael Pollastri

Appearances