New potent C2-Symmetric malaria plasmepsin I and II inhibitors Original Research Article

A series of malaria plasmepsin (Plm) I and II inhibitors containing a C2-symmetric core structure have been synthesised and tested for protease inhibition activity. These compounds can be prepared using a straightforward synthesis involving a phenol nucleophilic ring opening of a diepoxide. Exemplar compounds synthesised exhibited remarkable inhibitory activity against both Plm I and II, notably 15c with Ki values of 2.7 nM and 0.25 nM respectively, as well as showing >100-fold selectivity against Cathepsin D.