Alzheimer's disease (AD) is a progressive neurodegenerative disorder with multiple etiologies. Beta-amyloid (Aβ) self-aggregation and overexpression of class IIa histone deacetylases (HDACs) are strongly implicated with AD pathogenesis. In this study， a series of novel diarylheptanoid derivatives were designed， synthesized and evaluated for use as dual Aβ self-aggregation and class IIa HDAC inhibitors. Among these compounds， ， and displayed effective inhibitions for Aβ self-aggregation， HDAC5 activity and HDAC7 activity with IC values of <10 μM. The compounds contain three common features: (1) a catechol or pyrogallol moiety， (2) a carbonyl linker and (3) an aromatic ring that can function as an HDAC cap and create hydrophobic interactions with Aβ. Furthermore， compounds ， and showed no significant cytotoxicity to human neuroblastoma SH-SY5Y cells and also exhibited neuroprotective effect against HO-induced toxicity. Overall， these promising data highlighted compounds ， and as lead compounds that are worthy for further investigation.