Computational Molecular Modeling of Compounds from Amaryllidaceae Family as Potential Acetylcholinesterase Inhibitors

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 with AD.