Pyridinium cationic-dimer antimalarials, unlike chloroquine, act selectively between the schizont stage and the ring stage of Plasmodium falciparum

Mai Yoshikawa, Kazunori Motoshima, Kanji Fujimoto, Akihiro Tai, Hiroki Kakuta, Kenji Sasaki

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Malaria is a leading cause of death in developing countries, and the emergence of strains resistant to the main therapeutic agent, chloroquine, has become a serious problem. We have developed cationic-dimer type antimalarials, MAP-610 and PMAP-H10, which are structurally different from chloroquine. In this study, we introduced several substituents on the terminal phenyl rings of PMAP-H10. The electronic and hydrophobic properties of the substituents were correlated with the antimalarial activity and cytotoxicity of the compounds, respectively. Studies with synchronized cultures of malarial plasmodia showed that our cationic-dimers act selectively between the schizont stage and the ring stage of the parasitic cycle, unlike chloroquine, which has a stage-independent action. Thus, the mechanism of action of our antimalarials appears to be different from that of chloroquine, and our compounds may be effective against chloroquine-resistant strains.

Original languageEnglish
Pages (from-to)6027-6033
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number11
DOIs
Publication statusPublished - Jun 1 2008

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Keywords

  • Antimalarials
  • Cationic-dimer
  • Hammett's σ
  • Hansch-Fujita π
  • Synchronized culture

ASJC Scopus subject areas

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

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