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 journalArticle

3 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 Feb 15

Fingerprint

Astrocytes
ciclopirox
Hydrogen Peroxide
Toxicity
Derivatives
Oxidative stress
Scaffolds
Brain
Oxidative Stress
Mitochondrial Membrane Potential
Oxygen Consumption
Neurons
Deterioration
Assays
Cell Survival
Homeostasis
Cells
Oxygen
Membranes
Therapeutics

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

Cite this

Discovery of a novel series of N-hydroxypyridone derivatives protecting astrocytes against hydrogen peroxide-induced toxicity via improved mitochondrial functionality. / Singh, Sarbjit; Goo, Ja Il; Noh, Hyojin; Lee, Sung Jae; Kim, Myoung Woo; Park, Hyejun; Jalani, Hitesh B.; Lee, Kyeong; Kim, Chunsook; Kim, Won-Ki; Ju, Chung; Choi, Yongseok.

In: Bioorganic and Medicinal Chemistry, Vol. 25, No. 4, 15.02.2017, p. 1394-1405.

Research output: Contribution to journalArticle

Singh, Sarbjit ; Goo, Ja Il ; Noh, Hyojin ; Lee, Sung Jae ; Kim, Myoung Woo ; Park, Hyejun ; Jalani, Hitesh B. ; Lee, Kyeong ; Kim, Chunsook ; Kim, Won-Ki ; Ju, Chung ; Choi, Yongseok. / Discovery of a novel series of N-hydroxypyridone derivatives protecting astrocytes against hydrogen peroxide-induced toxicity via improved mitochondrial functionality. In: Bioorganic and Medicinal Chemistry. 2017 ; Vol. 25, No. 4. pp. 1394-1405.
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