Background: Alzheimer's disease (AD) is a neurodegenerative and irreversible disease that
inevitably progresses to the death. The usage of acetylcholinesterase (AChE) inhibitors has been effective
in reducing the symptoms of this disease. This study aims to examine the compounds from the species of
Amaryllidaceae family as a source for active compounds able to inhibit AChE and contribute to the
treatment of AD.
Methods: Molecular modeling was done with DFT/B3lyp/6-31G** method for the compounds: Galantamine,
Assoanine, Oxoassoanine, Epinorgalatamine, Hidroxygalantamine and Sanguinine. Potential
electrostatic maps and frontier orbital were calculated to investigate the likely sites of biological activity
of the compounds. The Pearson correlation was performed between the calculated descriptors and the
total energy to evaluate the descriptors that have better correlations. Similarly, correlation of the calculated
descriptors was performed with the hydration energy. Predictions of pharmacokinetic and toxicological
properties (mutagenicity and carcinogenicity) were obtained for the studied compounds.
Results: The molecule with the highest GAP was epinorgalantamine, which indicates greater stability and
lower reactivity than sanguinine that showed low stability and increased chemical reactivity. Sanguinine,
galantamine and epinorgalantamine molecules showed good pharmacokinetic results. Epinorgalantamine
and hidroxygalantamine did not exhibit mutagenicity.
Conclusion: Epinorgalantamine showed the most satisfactory pharmacokinetic and toxicological results
when compared to the parameters obtained from the other compounds investigated. However, more work
is still required so that, in the future, the use of natural compounds can contribute to the treatment of patients