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.The authors wish to acknowledge funding from the National Institute of Allergy and Infectious Diseases (MPP & MN: R01AI114685; MPP R21AI126296, R21AI127594; CRC: R21AI126296, R21AI133393. https://www.niaid.nih.gov/), the Spanish Ministerio de Economía, Industria y Competitividad, (MN: SAF2015-71444-P; DG-P: SAF2016-79957-R. http://www.mineco.gob.es), Junta de Andalucía (FG: CTS-7282. https://www.juntadeandalucia.es) and Subdirección General de Redes y Centros de Investigación Cooperativa (RICET) (MN: RD16/0027/0019; DG-P: RD16/0027/0014. https://bit.ly/2OegOnX). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe
