N10,N11-di-alkylamine indolo[3,2-b]quinolines as hemozoin inhibitors: Design, synthesis and antiplasmodial activity

Marta Figueiras, Lis Coelho, Kathryn J. Wicht, Sofia A. Santos, João Lavrado, Jiri Gut, Philip J. Rosenthal, Fátima Nogueira, Timothy J. Egan, Rui Moreira, Alexandra Paulo

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9 Citations (Scopus)


We recently reported that potent N10,O11-bis-alkylamine indolo[3,2-b]quinoline antimalarials act as hemozoin (Hz) growth inhibitors. To improve access and binding to the target we have now designed novel N10,N11-di-alkylamine bioisosteres. 3-Chloro derivatives (10a-f) showed selectivity for malaria parasite compared to human cells, high activity against Plasmodium falciparum chloroquine (CQ)-resistant strain W2 (IC50s between 20 and 158 nM), good correlation with β-hematin inhibition and improved vacuolar accumulation ratios, thus suggesting inhibition of Hz growth as one possible mechanism of action for these compounds. Moreover, our studies show that Hz is a valid target for the development of new antimalarials able to overcome CQ resistance.

Original languageEnglish
Pages (from-to)1530-1539
Number of pages10
JournalBioorganic & Medicinal Chemistry
Issue number7
Publication statusPublished - 1 Apr 2015


  • Hemozoin
  • Indolo[3 2-b]quinolines
  • Malaria
  • Resistance
  • Vacuolar accumulation

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