Synthesis and biological profiling of novel pyrazoles as antioxidant, antibacterial, and antimitotic agents: An in vitro and in silico approach

In this study, we report the synthesis and comprehensive characterization of a novel series of two Ethyl 3-Aryl-2-cyano-3-(3-hydroxy-5-methyl-1H-pyrazol-4-yl) propanoate derivatives 3a and 3b . The structural elucidation of these compounds was carried out using nuclear magnetic resonance ( 1 H & 13 C)-(NMR) spectroscopy and mass spectrometry. This study investigated the biological activities of two synthesized pyrazole derivatives, compounds 3a and 3b . Both showed moderate, dose-dependent antioxidant activity in the DPPH assay, with compound 3a exhibiting slightly better potency (IC 50 = 0.98 µmol/mL). Antibacterial evaluations revealed that compound 3b displayed strong activity against Staphylococcus aureus (inhibition zone: 18.9 mm; MIC = 1.25 µmol/mL), while compound 3a showed limited efficacy, especially against Gram-negative strains. In antimitotic assays, compound 3a demonstrated a moderate antigermination effect (20% inhibition), compared with 10% for compound 3b , consistent with their respective mitotic index results. Molecular docking studies revealed that both compounds 3a and 3b exhibit strong binding affinities toward antioxidant (Keap1), antibacterial (DNA gyrase), and antimitotic (tubulin) targets. Notably, 3a consistently showed superior interaction profiles, suggesting higher bioactivity potential across all targets. The binding stability of compound 3a with DNA gyrase and tubulin was further investigated and validated through molecular dynamics simulations. These findings suggest promising antioxidant and antibacterial potential, particularly for compound 3b , and notable antimitotic activity for compound 3a .