Figure 1.

Chemical structures of representative macrocyclic covalent proteasome inhibitors are shown on the right. Previously reported linear covalent or noncovalent macrocyclic inhibitors are shown on the left as a reference. The covalent electrophilic warhead leucine vinyl sulfone is colored red on each structure and the macrocycles are colored blue. EC₅₀ values represent the mean concentration required to inhibit P. falciparum asexual blood stage parasite growth by 50%.^9,11,16,17