Improvement of both plasmepsin inhibitory activity and antimalarial activity by 2-aminoethylamino substitution

We attached 2-aminoethylamino groups to allophenylnorstatine-containing plasmepsin (Plm) inhibitors and investigated SAR of the methyl or ethyl substitutions on the amino groups. Unexpectedly, compounds 22 (KNI-10743) and 25 (KNI-10742) exhibited extremely potent Plm II inhibitory activities (Ki <0.1 nM). Moreover, among our peptidomimetic Plm inhibitors, we identified the compounds with the highest antimalarial activity using a SYBR Green I-based fluorescence assay.

Attachments of 2-aminoethylamino substituents to an allophenylnorstatine-containing plasmepsin inhibitor enhanced both plasmepsin inhibitory and antimalarial activities.Figure optionsDownload as PowerPoint slide