Document Report Card
Basic Information
ID: ALA3877311
Journal: Bioorg Med Chem
Title: Discovery of a novel series of N-hydroxypyridone derivatives protecting astrocytes against hydrogen peroxide-induced toxicity via improved mitochondrial functionality.
Authors: Singh S, Goo JI, Noh H, Lee SJ, Kim MW, Park H, Jalani HB, Lee K, Kim C, Kim WK, Ju C, Choi Y.
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.
CiteXplore: 28089588