Synthesis, Structural Characterization, Antioxidant and Enzyme Inhibitory Activities of Novel Schiff Base Derivatives

Objectives: Schiff base derivatives have attracted considerable interest owing to their versatile biological properties and synthetic accessibility. The present study aimed to synthesize and characterize four novel azomethine derivatives and to investigate their antioxidant and enzyme inhibitory activities against α-amylase, α-glucosidase, and tyrosinase enzymes in order to evaluate their potential as multifunctional bioactive agents.Methods: Four Schiff base derivatives (Compounds 1–4) were synthesized via condensation reactions between substituted aniline derivatives and aliphatic or α,β-unsaturated aldehydes. The synthesized compounds were characterized by FT-IR, ^1H NMR, ^13C NMR, and ESI-MS analyses. Antioxidant activities were evaluated using DPPH, ABTS, CUPRAC, FRAP, phosphomolybdenum, and metal chelating assays. Enzyme inhibitory activities against α-amylase, α-glucosidase, and tyrosinase were determined spectrophotometrically and expressed as IC₅₀ values.Results: The synthesized compounds exhibited distinct structure-dependent biological profiles. Compound 2 demonstrated potent α-amylase and α-glucosidase inhibitory activities with IC₅₀ values comparable to those of acarbose, indicating promising antidiabetic potential. Compounds 3 and 4 displayed improved antioxidant activities, particularly in ABTS radical scavenging and reducing power assays, which may be attributed to the presence of the conjugated α,β-unsaturated side chain. Compound 4 exhibited the strongest tyrosinase inhibitory activity among the tested derivatives, whereas Compound 3 showed the most balanced antioxidant profile. Overall, para-chloro substitution favored carbohydrate-hydrolyzing enzyme inhibition, while extended conjugation enhanced antioxidant and anti-tyrosinase activities.Conclusion: The findings demonstrate that simple Schiff base scaffolds can generate diverse biological activities through subtle structural modifications. The identified structure-activity relationships suggest that para-chloro substituted derivatives may serve as promising antidiabetic candidates, whereas conjugated analogues may represent potential leads for antioxidant and anti-hyperpigmentation applications. Further studies are warranted to clarify their mechanisms of action and therapeutic potential.Keywords: α-Amylase inhibition; α-Glucosidase inhibition; Antioxidant activity; Schiff base derivatives; Structure-activity relationship; Tyrosinase inhibition.