Investigation of 7-benzylidenenaltrexone derivatives as resistance reverser for chloroquine-resistant Plasmodium chabaudi

Yoshinori Miyata, Hideaki Fujii, Yuka Uenohara, Seiki Kobayashi, Tsutomu Takeuchi, Hiroshi Nagase

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Derivatives of 7-benzylidenenaltrexone (BNTX), which was recently reported to be an effective chloroquine (CQ)-resistance reverser, were synthesized and evaluated for their CQ-resistance reversing activities. The synthesized derivatives showed CQ-resistance reversing effects. They also reacted with glutathione (GSH) both enzymatically and chemically, and inhibited glutathione reductase activity. 7-Benzyl derivative, which was obtained by reduction of the olefin group in α,β-unsaturated ketone structure of BNTX, also exhibited CQ-resistance reversing effect, but its potency was significantly lower than that of BNTX. These outcomes suggested that the decrease in GSH level could be one of the mechanisms of CQ-resistance reversing effects induced by BNTX derivatives.

Original languageEnglish
Pages (from-to)5174-5176
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number16
DOIs
Publication statusPublished - 2012 Aug 15

Fingerprint

Plasmodium chabaudi
Chloroquine
Derivatives
Glutathione Reductase
Alkenes
Ketones
Glutathione
7-benzylidenenaltrexone

Keywords

  • Chloroquine-resistance
  • Glutathione
  • Inhibition of glutathione reductase
  • Malaria
  • Resistance reversing effect

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Investigation of 7-benzylidenenaltrexone derivatives as resistance reverser for chloroquine-resistant Plasmodium chabaudi. / Miyata, Yoshinori; Fujii, Hideaki; Uenohara, Yuka; Kobayashi, Seiki; Takeuchi, Tsutomu; Nagase, Hiroshi.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 22, No. 16, 15.08.2012, p. 5174-5176.

Research output: Contribution to journalArticle

Miyata, Yoshinori ; Fujii, Hideaki ; Uenohara, Yuka ; Kobayashi, Seiki ; Takeuchi, Tsutomu ; Nagase, Hiroshi. / Investigation of 7-benzylidenenaltrexone derivatives as resistance reverser for chloroquine-resistant Plasmodium chabaudi. In: Bioorganic and Medicinal Chemistry Letters. 2012 ; Vol. 22, No. 16. pp. 5174-5176.
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