Structural Characterization and In Vitro and In Silico Studies on the Anti-α-Glucosidase Activity of Anacardic Acids from Anacardium occidentale

The growing focus on sustainable use of natural resources has brought attention to cashew nut shell liquid (CNSL), a by-product rich in anacardic acids (AAs) with potential applications in diabetes treatment. In this study, three different AAs from CNSL, monoene (15:1, AAn1), diene (15:2, AAn2), and triene (15:3, AAn3), and a mixture of the three (mix) were evaluated as <i>α</i>-glucosidase inhibitors. The samples were characterized by combining 1D and 2D NMR spectroscopy, along with ESI-MS. In vitro assays revealed that AAn1 had the strongest inhibitory effect (IC₅₀ = 1.78 ± 0.08 μg mL^-1), followed by AAn2 (1.99 ± 0.76 μg mL^-1), AAn3 (3.31 ± 0.03 μg mL^-1), and the mixture (3.72 ± 2.11 μg mL^-1). All AAs significantly outperformed acarbose (IC₅₀ = 169.3 μg mL^-1). In silico docking suggested that polar groups on the aromatic ring are key for enzyme-ligand binding. The double bond at C15, while not essential, enhanced the inhibitory effects. Toxicity predictions classified AAs as category IV, and pharmacokinetic analysis suggested moderately favorable drug-like properties. These findings highlight AAs as a promising option in the search for new hypoglycemic compounds.