Squaric acid/4-aminoquinoline conjugates: novel potent antiplasmodial agents

  • Eur J Med Chem. 2013 Nov:69:365-72. doi: 10.1016/j.ejmech.2013.08.037.
Carlos J A Ribeiro  1 ,  S Praveen Kumar ,  Jiri Gut ,  Lídia M Gonçalves ,  Philip J Rosenthal ,  Rui Moreira ,  Maria M M Santos
Affiliations
  • 1. Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon. Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
PMID: 24077527 DOI: 10.1016/j.ejmech.2013.08.037
Abstract

We report the synthesis and structure-activity relationship (SAR) analysis of a series of hybrid compounds containing a squaric moiety conjugated with heterocyclic moieties from well-known antimalarials. This novel series of compounds presents improved antiplasmodial activity compared with the squaric derivatives described in our previous work. Three compounds, 8b (IC₅₀ = 99 nM), 8c (IC₅₀ = 95 nM), and 8d (IC₅₀ = 105 nM) had greater in vitro potency than chloroquine 1 (IC₅₀ = 140 nM) against chloroquine resistant Plasmodium falciparum. In addition, they were noncytotoxic against NIH 3T3 and Hek 293T cells.

Keywords
4-Aminoquinoline; Antiplasmodial activity; Hybrid; Malaria; Squaramide.