Document Report Card

Basic Information

ID: ALA1687894

Journal: Eur J Med Chem

Title: Design, synthesis and evaluation of 3-methylene-substituted indolinones as antimalarials.

Authors: Praveen Kumar S, Gut J, Guedes RC, Rosenthal PJ, Santos MM, Moreira R.

Abstract: 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 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.

CiteXplore: 21295887

DOI: 10.1016/j.ejmech.2011.01.008