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 journalArticle

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

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Adenosylhomocysteinase
parasites
Antimalarials
Hydrolases
inhibitors
enzymes
Parasites
Derivatives
ribose
synthesis
Ribose
Cyclization
Enzymes
Plasmodium falciparum
Assays
5'-methylenearisteromycin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)

Cite this

Synthesis of 5′-methylenearisteromycin and its 2-fluoro derivative with potent antimalarial activity due to inhibition of the parasite S-adenosylhomocysteine hydrolase. / Takagi, Chieko; Sukeda, Makoto; Kim, Hye-Sook; Wataya, Yusuke; Yabe, Saori; Kitade, Yukio; Matsuda, Akira; Shuto, Satoshi.

In: Organic and Biomolecular Chemistry, Vol. 3, No. 7, 07.04.2005, p. 1245-1251.

Research output: Contribution to journalArticle

Takagi, Chieko ; Sukeda, Makoto ; Kim, Hye-Sook ; Wataya, Yusuke ; Yabe, Saori ; Kitade, Yukio ; Matsuda, Akira ; Shuto, Satoshi. / Synthesis of 5′-methylenearisteromycin and its 2-fluoro derivative with potent antimalarial activity due to inhibition of the parasite S-adenosylhomocysteine hydrolase. In: Organic and Biomolecular Chemistry. 2005 ; Vol. 3, No. 7. pp. 1245-1251.
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