Xueli Wang, See-Lok Ho, Chung-Yan Poon, Ting Yan, Hung-Wing Li* and Man Shing Wong* Pages 836 - 842 ( 7 )
Background: Xanthohumol has been reported to have cytoprotection through activation of Nrf2−ARE signaling pathway and; it has capability of scavenging free radicals, suggesting its potential for the prevention of neurodegeneration. However, the bio-incompatibility and blood-brain barrier impermeability of xanthohumol hindered its in vivo efficacy potential for treating Alzheimer’s disease (AD). <p></p> Objective: We designed and prepared a series of xanthohumol derivatives to enhance the desirable physical, biological and pharmacological properties in particular the blood-brain barrier permeability for intervention of AD. <p></p> Methods: We designed and synthesized a novel series of 9 xanthohumol derivatives. Their inhibitory effect on amyloid-β (1-42), Aβ1-42, oligomerization and fibrillation as well as neuroprotection against amyloid-β induced toxicities, were explored. <p></p> Results: Among the 9 xanthohumol derivatives, some of them exhibited a moderate to high inhibitory effect on Aβ1-42 oligomerization and fibrillation. They were biocompatible and neuroprotective to the SH-SY5Y cells by reducing the ROS generation and calcium uploading that were induced by the amyloid- β. Importantly, two of the derivatives were found to be blood-brain barrier permeable showing promising potential for AD treatment. <p></p> Conclusion: Two derivatives have been identified to be biocompatible, non-toxic, neuroprotective against Aβ-induced toxicities and blood-brain barrier permeable highlighting their promising potential as AD drug candidates for future clinical use.
Derivatives of xanthohumol, neuroprotective, amyloid aggregation inhibition, blood-brain barrier permeable.
Department of Chemistry, Hong Kong Baptist University, Hong Kong, SAR, Department of Chemistry, Hong Kong Baptist University, Hong Kong, SAR, Department of Chemistry, Hong Kong Baptist University, Hong Kong, SAR, Department of Chemistry, Hong Kong Baptist University, Hong Kong, SAR, Department of Chemistry, Hong Kong Baptist University, Hong Kong, SAR, Department of Chemistry, Hong Kong Baptist University, Hong Kong, SAR