Attachment of Basic Amino Group to Plasmepsin Inhibitors Exhibiting Potent Antimalarial Activity

摘要

Plasmepsin (Plm) is a target for new antimalarial drugs, but most reported Plm inhibitors have relatively low antimalarial activities. So, we attached substituents on a structure of the highly potent Plm inhibitor KNI-10006. Among the derivatives, amino-substituted compound such as KNI-10538 exhibited enhanced antimalarial activity maintaining potent Plm II inhibitory activity. These results suggest that auxiliary substituents of specific basic group contribute to deliver the inhibitors to the target Plm. We further synthesized the alkylamino derivatives.