Integrated synthesis, antiproliferative potential, and <i>in silico</i> analysis of novel pyrazole-based hydrazones derived from 3-(2-(4-chlorophenyl)hydrazineylidene)-5-phenylfuran-2(3 <i>H</i> )-one

Azofuranone was transformed into a series of pyrazole-based hydrazones with 71-79% yields through hydrazinolysis using hydrazine hydrate at room temperature followed by condensation with selected aromatic aldehydes in refluxing ethanol. The antiproliferative activity of the obtained derivatives was evaluated against MCF-7 (breast) and HCT-116 (colon) cancer cell lines using the MTT assay. Among the tested compounds, the chlorobenzylidene derivative (3a) exhibited the most pronounced cytotoxic activity (IC₅₀ = 6.33 ± 1.3 µM against HCT-116 and IC₅₀ = 8.61 ± 1.6 µM against MCF-7), while the remaining hydrazones also showed moderate to strong effects in both cell models. Computational target predictions suggested possible involvement of kinase-related pathways. Molecular docking studies were performed using CDK2 (PDB ID: 2 A4L) to explore potential binding modes. Compound 3a displayed a favorable docking score compared with the reference ligands and formed hydrogen-bond interactions with key residues within the active site. Molecular dynamics simulations indicated stable ligand-protein interaction patterns over the simulation period. In addition, <i>in silico</i> ADME analysis revealed acceptable physicochemical and pharmacokinetic characteristics, with compound 3a demonstrating the most balanced profile. Overall, the combined biological and computational findings identify compound 3a as a promising scaffold for further optimization in the development of antiproliferative agents.