Orally active, antimalarial, anticancer, artemisinin-derived trioxane dimers with high stability and efficacy

Gary H. Posner, Ik Hyeon Paik, Surojit Sur, Andrew J. McRiner, Kristina Borstnik, Suji Xie, Theresa A. Shapiro

Research output: Contribution to journalArticle

Abstract

In only two steps and in 70% overall yield, naturally occurring trioxane artemisinin (1) was converted on a gram scale into C-10-carba trioxane dimer 3. This new, very stable dimer was then transformed easily in one additional step into four different dimers 4-7. Alcohol and diol dimers 4 and 5 and ketone dimer 7 are 10 times more antimalarially potent in vitro than artemisinin (1), and alcohol and diol dimers 4 and 5 are strongly growth inhibitory but not cytotoxic toward several human cancer cell lines. Water-soluble carboxylic acid derivatives 8a and 9 were easily prepared in one additional step from dimers 4 and 5. Carboxylic acid dimers 8a and 9 are thermally stable even at 60 °C for 24 h, are more orally efficacious as antimalarials in rodents than either artelinic acid or sodium artesunate, and are strongly inhibitory but not cytotoxic toward several human cancer cell lines.

Original languageEnglish (US)
Pages (from-to)1060-1065
Number of pages6
JournalJournal of medicinal chemistry
Volume46
Issue number6
DOIs
StatePublished - Mar 13 2003

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Fingerprint Dive into the research topics of 'Orally active, antimalarial, anticancer, artemisinin-derived trioxane dimers with high stability and efficacy'. Together they form a unique fingerprint.

  • Cite this