The design, synthesis and evaluation of 3-methylene-substituted indolinones as falcipain inhibitors and antiplasmodial agents are described. These compounds react readily with thiols via an addition-elimination mechanism, indicating their potential as cysteine protease inhibitors. Several indolinones containing a Leu-i-amyl recognition moiety were found to be moderate inhibitors of the Plasmodium falciparum cysteine protease falcipain-2, but not of ...