Small-molecular inhibitors of Ca2+-induced mitochondrial permeability transition (MPT) derived from muscle relaxant dantrolene

Shinpei Murasawa, Katsuya Iuchi, Shinichi Sato, Tomomi Noguchi-Yachide, Mikiko Sodeoka, Tsutomu Yokomatsu, Kosuke Dodo, Yuichi Hashimoto, Hiroshi Aoyama

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

A structure consisting of substituted hydantoin linked to a 5-(halophenyl)furan-2-yl group via an amide bond was identified as a promising scaffold for development of low-molecular-weight therapeutic agents to treat vascular dysfunction, including ischemia/reperfusion injury. Among the compounds synthesized, 5-(3,5-dichlorophenyl)-N-{2,4-dioxo-3-[(pyridin-3-yl)methyl] imidazolidin-1-yl}-2-furamide (17) possessed the most potent inhibitory activity against Ca2+-induced mitochondrial swelling. The structural development, synthesis and structure-activity relationship of these compounds are described.

Original languageEnglish
Pages (from-to)6384-6393
Number of pages10
JournalBioorganic and Medicinal Chemistry
Volume20
Issue number21
DOIs
Publication statusPublished - 2012 Nov 1
Externally publishedYes

Keywords

  • Cyclophilin A
  • Cyclophilin D
  • Dantrolene
  • Ischemia/reperfusion
  • Mitochondrial permeability transition (MPT)
  • Mitochondrial swelling

ASJC Scopus subject areas

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

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