Our
previous study had identified ciclopirox (CPX) as a promising
lead compound for treatment of ischemic stroke. To find better neuroprotective
agents, a series of N-hydroxypyridone derivatives
based on CPX were designed, synthesized, and evaluated in this study.
Among these derivatives, compound 11 exhibits significant
neuroprotection against oxygen glucose deprivation and oxidative stress-induced
injuries in neuronal cells. Moreover, compound 11 possesses
good blood–brain barrier permeability and superior antioxidant
capability. In addition, a complex of compound 11 with
olamine11·Ola possesses good water solubility,
negligible hERG inhibition, and superior metabolic stability. The
in vivo experiment demonstrates that 11·Ola significantly
reduces brain infarction and alleviates neurological deficits in middle
cerebral artery occlusion rats. Hence, compound 11·Ola is identified in our research as a prospective prototype in the
innovation of stroke treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.