Bioactivity of Aminoantpyrine Heterocycles: Anti‐Inflammatory, Antibiofilm and Antioxidant Activities, and Admet Predictions

Heterocyclic cores remain fundamental in medicinal chemistry due to their ability to generate diverse pharmacological responses. In this study, a novel series of aminoantipyrine‐derived pyrazolone compounds (I–V) was synthesized in good yields (55%–82%). The antioxidant activity evaluated by DPPH and metal chelation assay revealed that compound V exhibited the most potent radical scavenging and metal chelation activity among the series, with an IC 50 value of 31.12 µg/mL, and also demonstrated strong Fe 2 + chelation capacity 94.0% at 400 µg/mL concentration, comparable to EDTA (99.0%). Antibiofilm and antimicrobial activity were assessed against Staphylococcus aureus ATCC25923 and Escherichia coli ATCC25922. In antibiofilm assays, compound III demonstrated moderate activity against Gram‐positive (57.6%), while limited activity (32.3%) against Gram‐negative. In DNA cleavage studies using pBR322 plasmid DNA, the compounds showed negligible effects at 1 mM but induced partial, concentration‐dependent DNA damage at 5 mM. However, MIC tests revealed that all compounds lacked significant antimicrobial activity against the tested bacterial panel, with MIC values of 5 and 7.5 mM. In silico ADMET analysis indicated that compound V possesses a balanced pharmacokinetic (PK) profile. Overall, compound V emerges as a promising antioxidant candidate with favorable PK properties, while compound III stands out as a potential antibiofilm agent.