New neplanocin analogues. 12. Alternative synthesis and antimalarial effect of (6′R)-6′-C-methylneplanocin A, a potent AdoHcy hydrolase inhibitor

Satoshi Shuto, Noriaki Minakawa, Satoshi Niizuma, Hye Sook Kim, Yusuke Wataya, Akira Matsuda

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32 Citations (Scopus)

Abstract

An improved method for the synthesis of (6′R)-6′-C-methylneplanocin A (RMNPA, 2), a potent S-adenosyl-L-homocysteine (AdoHcy) hydrolase inhibitor, was developed via a chelation-controlled stereoselective addition of MeTiCl3 to the neplanocin A 6′-aldehyde derivative 6. Compound 2 effectively inhibited the growth of malaria parasites both in vitro and in vivo. The antimalarial EC50 value of 2 against Plasmodium berghei in mice was 1.0 mg/kg/day, which was superior to that of chloroquine (EC50 = 1.8 mg/kg/day).

Original languageEnglish
Pages (from-to)748-751
Number of pages4
JournalJournal of medicinal chemistry
Volume45
Issue number3
DOIs
Publication statusPublished - Jan 31 2002

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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