Background: Alzheimer's disease (AD) involves an irreversible and progressive
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 chalcones
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 physicochemical
properties using SwissADME software.
Results: We found that the majority of the chalcones have been tested against cholinesterases,
with moderate to good potencies, but in recent years, the number of publications
related to targets of the amyloid hypothesis has been growing. Regarding the physicochemical
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 examples
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.