Design, Synthesis, and Evaluation of Multitarget-Directed Selenium-Containing Clioquinol Derivatives for the Treatment of Alzheimer's Disease

作者：Wang, Zhiren; Wang, Yali; Li, Wenrui; Mao, Fei; Sun, Yang; Huang, Ling^*; Li, Xingshu

来源：ACS Chemical Neuroscience, 2014, 5(10): 952-962.

DOI：10.1021/cn500119g

• Alzheimers disease
• selenium-containing clioquinol derivatives
• antioxidative properties
• inhibition of metal-induced A beta aggregation

A series of selenium-containing clioquinol derivatives were designed, synthesized, and evaluated as multifunctional anti-Alzheimer's disease (AD) agents. In vitro examination showed that several target compounds exhibited activities such as inhibition of metal-induced A beta aggregation, antioxidative properties, hydrogen peroxide scavenging, and the prevention of copper redox cycling. A parallel artificial membrane permeation assay indicated that selenium-containing clioquinol derivatives possessed significant blood-brain barrier (BBB) permeability. Compound 8a, with a propynylselanyl group linked to the oxine, demonstrated higher hydrogen peroxide scavenging and intracellular antioxidant activity than clioquinol. Furthermore, 8a exhibited significant inhibition of Cu(II)-induced A beta 1-42 aggregation and was capable of disassembling the preformed Cu(II)-induced A beta aggregates. Therefore, 8a is an excellent multifunctional promising compound for development of novel drugs for AD.

• 出版日期2014-10
• 单位中山大学