Novel squaramides with in vitro liver stage antiplasmodial activity

  • Bioorg Med Chem. 2016 Apr 15;24(8):1786-92. doi: 10.1016/j.bmc.2016.03.005.
Carlos J A Ribeiro  1 ,  Margarida Espadinha  1 ,  Marta Machado  2 ,  Jiri Gut  3 ,  Lídia M Gonçalves  1 ,  Philip J Rosenthal  3 ,  Miguel Prudêncio  2 ,  Rui Moreira  1 ,  Maria M M Santos  4
Affiliations
  • 1. Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal.
  • 2. Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal.
  • 3. Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA 94143, USA.
  • 4. Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal. Electronic address: [email protected].
PMID: 26968650 DOI: 10.1016/j.bmc.2016.03.005
Abstract

A structure-activity relationship study was performed with ten 8-aminoquinoline-squaramides compounds active against liver stage malaria parasites, using human hepatoma cells (Huh7) infected by Plasmodium berghei parasites. In addition, their blood-schizontocidal activity was assessed against chloroquine-resistant W2 strain Plasmodium falciparum. Compound 3 was 7.3-fold more potent than the positive control primaquine against liver-stage parasites, illustrating the importance of the squarate moiety to activity.

Keywords
8-Aminoquinoline; Antiplasmodial activity; Liver stage; Malaria; Squaramide.