An in silico assay was designed, and generated compounds were studied to delimitate the synthesis by microwave irradiation–conventional heat combination. In vitro evaluation as antihyperglycemic and hypoglycemic agents were made, where 2s has good potential.

Background/Objectives: Parmentiera edulis, traditionally called “cuajilote”, is a medicinal plant used to treat infections, indigestion, kidney problems, and diabetes. Although all parts of the plant are utilized, there is little scientific evidence available on its phytochemical composition to explain its medicinal properties. This exploratory study aims to characterize and identify phytochemicals in hydromethanolic extracts of leaves, stems, and fruits; determine their antioxidant capacity, and evaluate in vitro and in silico inhibition of α-glucosidase and α-amylase, enzymes involved in glycemic control. Methods: Total phenolic and flavonoid contents were determined, and antioxidant capacity was evaluated using different assays. Phenolic acids were tentatively identified by UPLC-qTOF-MS/MS. Enzyme inhibition assays against α-glucosidase and α-amylase were performed in vitro, and molecular docking was used to explore enzyme–ligand interactions. Results: The total phenolic content was significantly higher in the fruit (552.9 mg GAE/100 g dw), while flavonoids were more abundant in leaves (119.84 mg QE/100 g dw). Antioxidant capacity varied among plant parts, depending on the assay used. Caffeic, chlorogenic, coumaric, ferulic, gallic, and quinic acids were identified. The highest concentrations were observed for chlorogenic, ferulic, and quinic acids. Among the analyzed parts, leaf extracts showed the most potent inhibitory effect on α-glucosidase (IC₅₀: 0.85 mg/mL) and α-amylase (IC₅₀: 1.38 mg/mL). Molecular docking revealed that chlorogenic and quinic acids interacted with the catalytic sites of α-amylase (Glu233, Asp197, and Asp300), whereas in α-glucosidase, interactions were observed at allosteric sites. Conclusions: These results suggest that Parmentiera edulis possesses bioactive compounds that could explain its therapeutic use.