Discovery of a novel series of N-hydroxypyridone derivatives protecting astrocytes against hydrogen peroxide-induced toxicity via improved mitochondrial functionality

Sarbjit Singh, Ja Il Goo, Hyojin Noh, Sung Jae Lee, Myoung Woo Kim, Hyejun Park, Hitesh B. Jalani, Kyeong Lee, Chunsook Kim, Won Ki Kim, Chung Ju, Yongseok Choi

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Astrocytes play a key role in brain homeostasis, protecting neurons against neurotoxic stimuli such as oxidative stress. Therefore, the neuroprotective therapeutics that enhance astrocytic functionality has been regarded as a promising strategy to reduce brain damage. We previously reported that ciclopirox, a well-known antifungal N-hydroxypyridone compound, protects astrocytes from oxidative stress by enhancing mitochondrial function. Using the N-hydroxypyridone scaffold, we have synthesized a series of cytoprotective derivatives. Mitochondrial activity assay showed that N-hydroxypyridone derivatives with biphenyl group have comparable to better protective effects than ciclopirox in astrocytes exposed to H2O2. N-hydroxypyridone derivatives, especially 11g, inhibited H2O2-induced deterioration of mitochondrial membrane potential and oxygen consumption rate, and significantly improved cell viability of astrocytes. The results indicate that the N-hydroxypyridone motif can provide a novel cytoprotective scaffold for astrocytes via enhancing mitochondrial functionality.

Original languageEnglish
Pages (from-to)1394-1405
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume25
Issue number4
DOIs
Publication statusPublished - 2017

Keywords

  • Astrocytes
  • Ciclopirox
  • N-hydroxypyridone
  • Neuroprotection
  • Oxidative stress

ASJC Scopus subject areas

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

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