Orally active, water-soluble antimalarial 3-aryltrioxanes: Short synthesis and preclinical efficacy testing in rodents

Gary H. Posner, Heung Bae Jeon, Poonsakdi Ploypradith, Ik Hyeon Paik, Kristina Borstnik, Suji Xie, Theresa A. Shapiro

Research output: Contribution to journalArticlepeer-review

Abstract

Short chemical syntheses of four new antimalarial trioxanes are presented, starting with inexpensive and commercially available cyclohexanone. Almost exclusive formation of the trioxane 12α-stereoisomers simplifies product purification. Carboxyphenyltrioxanes 3 and 5 are thermally stable in air even at 60°C for 24 h. When administered orally, these new carboxyphenyltrioxanes are highly efficacious in curing malaria-infected mice. Important for their practical in vivo administration, these new synthetic antimalarial trioxanes 3 and 5 are 14-20 times more soluble in water at pH 7.4 than is artelinic acid (1), a leading semisynthetic, herb-derived antimalarial trioxane drug candidate.

Original languageEnglish (US)
Pages (from-to)3824-3828
Number of pages5
JournalJournal of medicinal chemistry
Volume45
Issue number18
DOIs
StatePublished - Aug 29 2002

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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