Kumar, S. PraveenGut, JiriGuedes, Rita C.Rosenthal, Philip J.Santos, Maria M. M.Moreira, Rui2011-08-032011-08-032011Kumar, S. Praveen; Gut, Jiri; Guedes, Rita C. ; Rosenthal, Philip J.; Santos, Maria M. M.; Moreira, Rui. Design, synthesis and evaluation of 3-methylene-substituted indolinones as antimalarials, European Journal of Medicinal Chemistry, 46, 927-933, 2011.0223-5234http://dx.doi.org/10.1016/j.ejmech.2011.01.008http://hdl.handle.net/10451/3860The 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 the related protease falcipain-3, and displayed antiplasmodial activity against the chloroquine-resistant P. falciparum W2 strain in the low micromolar range. Coupling a 7-chloroquinoline moiety to the 3-methylene-substituted indolinone scaffold led to a significant improvement in antiplasmodial activity.engIndolin-2-onesFalcipain inhibitorAntiplasmodial activityMalariajournal article2011-07-01