Bis-alkylamine quindolone derivatives as new antimalarial leads

J, Lavrado , K, Gani , PA, Nobre , SA, Santos , P Figueiredo , Dinora Ferreira, Virgilio Estólio do Rosário, J, Gut , PJ, Rosenthal , R, Moreira , A. Paulo

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22 Citations (Scopus)

Abstract

Quindolone derivatives, designed to target the malaria parasite digestive vacuole and heme detoxification pathway, have been synthesized by reaction with 2-chloro-N,N-diethylethanamine. This reaction gave N,O-, N,N- and O-alkylated products containing one or two basic side-chains. The compounds were evaluated for antiplasmodial activity against the chloroquine-resistant Plasmodium falciparum W2 strain and for cytotoxicity in HepG2 A16 hepatic cells. By incorporating alkylamine side chains and chlorine atoms in the quindolone nucleus we transformed the inactive tetracyclic parent quindolones into moderate or highly active and selective antimalarial compounds. The most active and selective compound, 5c, showed an IC50 = 51 nM for P. falciparum and a selectivity ratio of 98. (C) 2010 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)5634-5637
Number of pages4
JournalBioorganic & Medicinal Chemistry Letters
VolumeVol. 20
Issue numbern.º 19
DOIs
Publication statusPublished - 1 Oct 2010

Keywords

  • Indoloquinoline
  • Antiplasmodial
  • Malaria
  • Digestive vacuole
  • Hemozoin

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