Zang_2023_Eur.J.Med.Chem_265_116070

Alzheimer's disease (AD) is the most common neurodegenerative disease among the elderly. Contemporary treatments can only relieve symptoms but fail to delay disease progression. Curcumin is a naturally derived compound that has demonstrated significant therapeutic effects in AD treatment. Recently, molecular hybridization has been utilized to combine the pharmacophoric groups present in curcumin with those of other AD drugs, resulting in a series of novel compounds that enhance the therapeutic efficacy through multiple mechanisms. In this review, we firstly provide a concise summary of various pathogenetic hypotheses of AD and the mechanism of action of curcumin in AD, as well as the concept of molecular hybridization. Subsequently, we focus on the recent development of hybrid molecules derived from curcumin, summarizing their structures and pharmacological activities, including cholinesterase inhibitory activity, Abeta aggregation inhibitory activity, antioxidant activity, and other activities. The structure-activity relationships were further discussed.