FURAN-BASED CHALCONE DERIVATIVES: SYNTHESIS, ANTIOXIDANT EVALUATION, DFT CALCULATIONS AND ADME PREDICTIONS

Heteroaromatic chalcones have attracted attention due to their structural versatility and redox-related properties. In this study, five furanochalcones with distinct aromatic substitution patterns were synthesized by ultrasound-assisted Claisen-Schmidt condensation and characterized by 1H and 13C NMR spectroscopy. Antioxidant activity was evaluated using DPPH• radical scavenging and phosphomolybdenum assays, while pharmacokinetic and electronic properties were investigated using SwissADME and ProTox 3.0, while electronic properties were investigated by Density Functional Theory (DFT). In the DPPH• assay, compound 3 exhibited the highest activity among the synthesized derivatives at 1-10 mmol L-1, whereas compound 5 (2-OH,5-NO2) showed the lowest estimated IC50 (16.02 mmol L-1) and the highest activity at 20 mmol L-1 (58.99%). In the phosphomolybdenum assay at 10 mmol L-1, compound 5 showed the highest relative antioxidant activity (68.46%). DFT calculations using SMD(ethanol)/B3LYP/def2-TZVP revealed substituent-dependent electronic differences, with compound 3 exhibiting the lowest HOMO-LUMO gap (3.30 eV) and global hardness (1.65 eV), and the highest electrophilicity (6.15 eV). O-H bond dissociation enthalpies were 89.84 and 95.85 kcal mol-1 for compounds 2 and 5, respectively, indicating that O-H bond strength alone does not explain the DPPH• response. HAT and SET processes are therefore considered plausible mechanistic contributions. In silico ADME predictions indicated compliance with classical drug-likeness criteria and predicted high gastrointestinal absorption. Overall, the results provide preliminary insights into the structure-activity relationships of these furanochalcones and support further investigation in biological models.