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

Authors
Singh, SarbjitGoo, Ja-IlNoh, HyojinLee, Sung JaeKim, Myoung WooPark, HyejunJalani, Hitesh B.Lee, KyeongKim, ChunsookKim, Won-KiJu, ChungChoi, Yongseok
Issue Date
15-2월-2017
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Keywords
Ciclopirox; N-hydroxypyridone; Astrocytes; Oxidative stress; Neuroprotection
Citation
BIOORGANIC & MEDICINAL CHEMISTRY, v.25, no.4, pp.1394 - 1405
Indexed
SCIE
SCOPUS
Journal Title
BIOORGANIC & MEDICINAL CHEMISTRY
Volume
25
Number
4
Start Page
1394
End Page
1405
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/84434
DOI
10.1016/j.bmc.2016.12.052
ISSN
0968-0896
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 membrane-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. (C) 2017 Elsevier Ltd. All rights reserved.
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생명과학대학 (생명공학부)
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