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

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

Volume: 28 Issue: 21

Author(s): Giorgio Antoniolli, Wanda P. Almeida*, Camila C. Frias and Tiago B. de Oliveira

Affiliation:

• Faculty of Pharmaceutical Sciences, University of Campinas, Campinas, São Paulo, Brazil; 3Federal Institute of Alagoas, Campus Maragogi, Alagoas,Brazil

Keywords: chalcones, Alzheimer's disease, cholinesterases, amyloid, BACE-1, physicochemical properties.

Abstract:

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.

Cite this article as:

Antoniolli Giorgio , Almeida P. Wanda *, Frias C. Camila and de Oliveira B. Tiago , Chalcones Acting as Inhibitors of Cholinesterases, β-Secretase and β- Amyloid Aggregation and other Targets for Alzheimer’s Disease: A Critical Review, Current Medicinal Chemistry 2021; 28 (21) . https://dx.doi.org/10.2174/0929867327666201020151804