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

doi:10.1021/jm010374i

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

Research output: Contribution to journal › Article › peer-review

33 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 language	English
Pages (from-to)	748-751
Number of pages	4
Journal	Journal of medicinal chemistry
Volume	45
Issue number	3
DOIs	https://doi.org/10.1021/jm010374i
Publication status	Published - Jan 31 2002

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/jm010374i

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

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).",

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AU - Shuto, Satoshi

AU - Minakawa, Noriaki

AU - Niizuma, Satoshi

AU - Kim, Hye Sook

AU - Wataya, Yusuke

AU - Matsuda, Akira

PY - 2002/1/31

Y1 - 2002/1/31

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AB - 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).

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

Abstract

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