Chalcones Acting as Inhibitors of Cholinesterases, β-Secretase and β-Amyloid Aggregation and other Targets for Alzheimer's Disease: A Critical Review

Background: Alzheimer's disease (AD) involves an irreversible and progres-sive neurodegeneration, with multifactorial pathophysiology, including the cholinergic deficit, amyloid plaques, neurofibrillary tangles, oxidative stress, and neurodegeneration. Despite the severity of the disease, the therapeutic arsenal is limited, arousing the interest of researchers to search for substances that can act on these markers. Objective: In this review, we highlight some relevant points, such as the ability of chal-cones to act on different targets related to the pathophysiology of Alzheimer's disease; cholinesterases, amyloid peptide, beta-secretase and other biomarkers. Method: This mini-review covered the literature concerning chalcones bioactivity from 2010 until now. In addition to the theoretical review, we included the prediction of physi-cochemical properties using SwissADME software. Results: We found that the majority of the chalcones have been tested against cho-linesterases, with moderate to good potencies, but in recent years, the number of publica-tions related to targets of the amyloid hypothesis has been growing. Regarding the physic-ochemical properties, chalcones have a good profile, except for the water solubility, which is not favorable. Conclusion: The most important characteristic of these molecules is that many of the ex-amples mentioned here act on more than one target, characterizing them as multi-target compounds. Regarding predicted properties, solubility stands out as the most problematic one; however, these structures can incorporate functional groups that circumvent this problem of solubility without interfering in the biological activity.