The survival times of malaria-infected mice are prolonged more by several new two-carbon-linked artemisinin-derived dimer carbamates than by the trioxane antimalarial drug artemether

Ryan C. Conyers, Jennifer R. Mazzone, Maxime A. Siegler, Abhai K. Tripathi, David J. Sullivan, Bryan T. Mott, Gary H. Posner

Research output: Contribution to journalArticlepeer-review

Abstract

Sixteen new artemisinin-derived 2-carbon-linked trioxane dimers were prepared to study chemical structure/antimalarial activity relationships (SAR). Administering a very low single oral dose of only 5 mg/kg of dimer secondary alcohol 6a or 6b plus 15 mg/kg of mefloquine hydrochloride prolonged the lives of Plasmodium berghei-infected mice to an average of 25 days after infection. This ACT chemotherapy result is of high medicinal significance because the antimalarial efficacy of the popular trioxane drug artemether (2) plus mefloquine under the same conditions was significantly lower (only 20 day average survival). NH-aryl carbamate derivatives 7e, 7i, and 7j of 2-carbon-linked dimer alcohol 6b also significantly outperformed artemether (2) in prolonging the survival times (25-27 days) of malaria-infected mice.

Original languageEnglish (US)
Pages (from-to)1285-1289
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume24
Issue number5
DOIs
StatePublished - Mar 1 2014

Keywords

  • Antimalarial chemotherapy
  • Oral bioavailability
  • Single oral dose ACT
  • Trioxane dimer carbamates

ASJC Scopus subject areas

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

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