GSK3 Inhibitors for the Treatment of Human African Trypanosomiasis

Abstract

 

 

 

Glycogen synthase kinase 3 (GSK3) is a genetically validated drug target for human African trypanosomiasis (HAT), also called African sleeping sickness.

 

 

We report the synthesis and biological evaluation of aminopyrazole derivatives as Trypanosoma brucei GSK3 short inhibitors. Low nanomolar inhibitors, which had high selectivity over the off-target human CDK2 and good selectivity over human GSK3β enzyme, have been prepared.

 

 

These potent kinase inhibitors with small molecular structure  demonstrated low micromolar levels of inhibition of the Trypanosoma brucei brucei parasite grown in culture.