New treatments are needed for neglected tropical diseases (NTDs) such as Human African
trypanosomiasis (HAT), Chagas disease, and schistosomiasis. Through a whole organism
high-throughput screening campaign, we previously identified 797 human kinase inhibitors
that grouped into 59 structural clusters and showed activity against T. brucei, the causative
agent of HAT. We herein report the results of further investigation of one of these clusters
consisting of substituted isatin derivatives, focusing on establishing structure-activity and
-property relationship scope. We also describe their in vitro absorption, distribution, metabolism, and excretion (ADME) properties. For one isatin, NEU-4391, which offered the best
activity-property profile, pharmacokinetic parameters were measured in mice