Borrelidin analogues with antimalarial activity: Design, synthesis and biological evaluation against Plasmodium falciparum parasites

Akihiro Sugawara, Toshiaki Tanaka, Tomoyasu Hirose, Aki Ishiyama, Masato Iwatsuki, Yoko Takahashi, Kazuhiko Otoguro, Satoshi Omura, Toshiaki Sunazuka

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Borrelidin, a structurally unique 18-membered macrolide, was found to express antimalarial activity against drug-resistant Plasmodium falciparum malaria parasites, with IC50 value of 0.93 ng/mL. However, it also displays strong cytotoxicity against human diploid embryonic MRC-5 cells. To investigate the issue of the cytotoxicity of borrelidin, borrelidin-based analogues were synthesized and their anti-Plasmodium properties were evaluated. In this communication, we report that a novel borrelidin analogue, bearing the CH2SPh moiety via a triazole linkage, was found to retain a potent antimalarial activity, against drug-sensitive and drug-resistant parasite strains, but possess only weak cytotoxicity against human cells.

Original languageEnglish
Pages (from-to)2302-2305
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number8
DOIs
Publication statusPublished - 2013 Apr 15
Externally publishedYes

Keywords

  • Antimalarial
  • Borrelidin
  • Malaria
  • Plasmodium falciparum
  • Structure-activity relationships

ASJC Scopus subject areas

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

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