A novel multi-target strategy to attenuate the progression of Parkinson's disease by diamine hybrid AGE/ALE inhibitor

FUTURE MEDICINAL CHEMISTRY(2021)

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摘要
Instead of a conventional 'one-drug-one-target approach', this article presents a novel multi-target approach with a concept of trapping simultaneously as many detrimental factors as possible involved in the progression of Parkinson's disease. These factors include reactive carbonyl species, reactive oxygen species, Fe3+/Cu2+ and ortho-quinones (o-quinone), in particular. Different from the known multi-target strategies for Parkinson's disease, it is a sort of 'vacuum cleaning' strategy. The new agent consists of reactive carbonyl species scavenging moiety and reactive oxygen species scavenging and metal chelating moiety linked by a spacer. Provided that the capacity of scavenging o-quinones is demonstrated, this type of agent can further broaden its potential therapeutic profile. In order to support this new hypothetical approach, a number of simple in vitro experiments are proposed.
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关键词
AGE/ALE inhibitor, methylglyoxal, ortho-quinone, Parkinson's disease, quinoxaline, RCS, ROS, alpha-synuclein
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