## 4 Conclusions  
In this work, we have presented a study that covers theoretical predictions from quantum chemistry to the molecular dynamics level, including molecular docking. The results presented here help to understand the interactions between acarbose and the new alternatives of treatment for diabetes, maysin and luteolin, with human maltase-glucoamylase (NtMGAM), as well as the oxidative damage in the maltase-glucoamylase. These predictions can also help to interpret existing results or to predict future experimental results.  
The dihedral angles present in the molecular structure of ACA, MAY, and LUT, as well as the possible steric impediments inside of the active site, were analyzed by geometry optimization calculations. Chemical reactivity parameters were necessary to determine the charge transfer distribution between ligands and amino acids of the active site in the maltase-glucoamylase. Moreover, the three couplings presented oxidative damage, being 45.4% for ACA and 100% for MAY and LUT. According to [PERSON], et al. [78], flavonoids are able to inhibit alpha-amylase enzymes by reducing postprandial glucose levels, which coincides with the theoretical values obtained for the oxidative damage in the LUT-NtMGAM coupling.  
According to values for the binding energy obtained from molecular docking analysis, MAY ligand presented the greatest facility to interact with NtMGAM. Additionally, the chemical reactivity for MAY ligand, suggested greater stability when this molecule accepts electrons from the amino acids, as well as a greater facility to modify its electronic configuration in the presence of the active site. However, it is well known that the acarbose drug (ACA) is the best strategy to decrease the postprandial rise in blood glucose and to prevent diabetes complications [79]. Therefore, an analysis that considers only direct interactions between ligands and the active site seems to be insufficient. In this sense, molecular dynamics simulations provided a complementary methodology that incorporates solvent and temperature effects not considered in molecular docking. Indeed, molecular dynamics showed that ACA is the molecule that displaces a bigger amount of water compared to LUT and MAY, which indicates the greater affinity of this ligand to the active site of NtMGAM. The obtained results for MAY and LUT coincided with reported experimental results, where was confirmed that phenolic compounds from maize silks can inhibit the activity of carbohydrate-hydrolyzing enzymes such as the intestinal \(\alpha\)-glucosidases, with similar or lower values of IC50 than acarbose. Since any ligand-binding process can displace water molecules from the binding site [78], it is recommended for future research to analyze ACA-like ligands that are not very hydrophilic.  
Formal analysis, L.-L.-M. and L.-M.R.-V.; investigation, L.-L.-M.; methodology, L.-L.-M. and J.P.P.-B.; writing--original draft, L.-L.-L.-M., J.P.P.-B. and L.-M.R.-V.; writing--review and editing, L.-L.L.-M., N.G.-M., J.P.P.-B., N.-A.S.-B., H.A.P.-C., M.A.C.-R., J.P.F.-D.I.R. and L.-M.R.-V. All authors have read and agreed to the published version of the manuscript.  
This research was funded by Programa para el Desarrollo Profesional Docente (PRODEP) by grant 18-6897.  
Not applicable.  
**Data Availability Statement:** The data presented in this study are available on request from the corresponding authors.  
**Acknowledgments:** [PERSON] thanks Programa para el Desarrollo Professional Docente for the grant. All the researchers are grateful to Universidad Autonoma de Chihuahua for the support and infrastructure provided.  
**Conflicts of Interest:** The authors declare no conflict of interest. The founding sponsors had no role in the design of the study, in the collection, analyses or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.