Synthesis of 5′-methylenearisteromycin and its 2-fluoro derivative with potent antimalarial activity due to inhibition of the parasite S-adenosylhomocysteine hydrolase

Chieko Takagi, Makoto Sukeda, Hye Sook Kim, Yusuke Wataya, Saori Yabe, Yukio Kitade, Akira Matsuda, Satoshi Shuto

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

5′-Methylenearisteromycin (5) and its 2-fluoro derivative 6, which were designed as antimalarial agents because of their AdoHcy hydrolase inhibition, were synthesized from D-ribose, using a stereoselective intramolecular radical cyclization as the key step to construct the carbocyclic structure. These compounds were evaluated as AdoHcy hydrolase inhibitors with the recombinant human and malarial parasite enzymes. Although 5 and 6 were both potent inhibitors of the malarial parasite AdoHcy hydrolase, the 2-fluoro derivative 6 proved to be superior due to its lower inhibitory effect on the human enzyme. In addition, 6 was identified as a potent antimalarial agent using an in vitro assay system with Plasmodium falciparum.

Original languageEnglish
Pages (from-to)1245-1251
Number of pages7
JournalOrganic and Biomolecular Chemistry
Volume3
Issue number7
DOIs
Publication statusPublished - Apr 7 2005

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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