Thiophene–benzothiazole based pyrazoline as a potential antioxidant and tyrosine kinase inhibitor: docking and DFT study

This study reports the synthesis of a novel pyrazoline-based thiophene–benzothiazole hybrid and the evaluation of its antioxidant activity. The target compound was obtained via a 3+2 cycloaddition approach starting from chalcones synthesized by the Claisen–Schmidt condensation of 4-(methylthio) benzaldehyde and 2-acetyl-5-bromothiophene, followed by cyclization with 2-hydrazinobenzothiazole. The structure of the synthesized pyrazoline derivative was confirmed using FT-IR, 1H NMR, 13C NMR, and DEPT-135 spectroscopic techniques. Antioxidant activity was assessed using the phosphomolybdenum assay and compared with ascorbic acid as a reference standard. The compound exhibited measurable antioxidant activity, with an IC50 of 121.65 µg/mL compared with 66.55 µg/mL for ascorbic acid, indicating lower antioxidant potency than the reference standard. Molecular docking against the EphB4 receptor tyrosine kinase (PDB ID: 3ZEW) was used as an exploratory assessment of a potential cancer-related interaction and was interpreted independently of the antioxidant response. DFT calculations at the B3LYP/6-311G(d,p) level provided complementary insight into the structural and electronic properties of the compound, without assigning the calculated electronic descriptors as direct mechanistic evidence of its antioxidant activity. Overall, the results provide preliminary insights into the structural and electronic features of the compound and its potential antioxidant behavior.