Parallel synthesis of 9-aminoacridines and their evaluation against chloroquine-resistant Plasmodium falciparum

Marc O. Anderson, John Sherrill, Peter B. Madrid, Ally P. Liou, Jennifer L. Weisman, Joseph L. DeRisi, R. Kiplin Guy

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


A parallel synthetic strategy to the 9-aminoacridine scaffold of the classical anti-malarial drug quinacrine (2) is presented. The method features a new route to 9-chloroacridines that utilizes triflates of salicylic acid derivatives, which are commercially available in a variety of substitution patterns. The route allows ready variation of the two diversity elements present in this class of molecules: the tricyclic aromatic heterocyclic core, and the disubstituted diamine sidechain. In this study, a library of 175 compounds was designed, although only 93 of the final products had purities acceptable for screening. Impurity was generally due to incomplete removal of 9-acridones (18), a degradation product of the 9-chloroacridine synthetic intermediates. The library was screened against two strains of Plasmodium falciparum, including a model of the drug-resistant parasite, and six novel compounds were found to have IC50 values in the low nanomolar range.

Original languageEnglish
Pages (from-to)334-343
Number of pages10
JournalBioorganic and Medicinal Chemistry
Issue number2
StatePublished - Jan 15 2006


  • Acridine
  • Malaria
  • Parallel synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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