Design, synthesis and evaluation of 4′-OH-flurbiprofen-chalcone hybrids as potential multifunctional agents for Alzheimer’s disease treatment

Publication date: Available online 2 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Zhongcheng Cao, Jie Yang, Rui Xu, Qin Song, Xiaoyu Zhang, Hongyan Liu, Xiaoming Qiang, Yan Li, Zhenghuai Tan, Yong Deng
A series of 4′-OH-flurbiprofen-chalcone hybrids were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease. The biological screening results indicated that most of these hybrids exhibited good multifunctional activities. Among them, compounds 7k and 7m demonstrated the best inhibitory effects on self-induced Aβ1-42 aggregation (60.0% and 78.2%, respectively) and Cu²⁺-induced Aβ1-42 aggregation (52.4% and 95.0%, respectively). Moreover, these two representative compounds also exhibited good antioxidant activities, MAO inhibitions, biometal chelating abilities and anti-neuroinflammatory activities in vitro. Furthermore, compound 7m displayed appropriate blood-brain barrier permeability. These multifunctional properties highlight compound 7k and 7m as promising candidates for further development of multi-functional drugs against AD.

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