Innovative Silica-Supported Acid Catalyst for Sustainable Synthesis of Bioactive Pyrazoles: Insights into Mechanisms and Applications

An innovative silica-bonded <i>N</i>-(propylaminobenzene)-sulfonic acid (SBPASA) catalyst was synthesized by immobilizing metanilic acid onto silica and characterized using advanced techniques, including FTIR, XRD, SEM/EDX, Raman spectroscopy, UV-visible analysis, and BET surface area analysis. The catalyst exhibited a high surface area of 306.9 m²/g, an optimal mesoporous diameter of 31.4 Å, and high product yields (up to 98%), distinguishing it from previously reported silica-supported catalysts. This catalyst facilitated the efficient preparation of 4,4'-(arylmethylene)-bis-(1<i>H</i>-pyrazol-5-ols) (<b>4a</b>-<b>i</b>) in a solvent-free environment, resulting in high yields with a variety of functional groups. The silica surface played a critical role in facilitating key reaction steps, including Michael addition, Knoevenagel condensation, and cyclization. The catalyst demonstrated remarkable recyclability, retaining its catalytic activity up to six consecutive cycles without significant loss in efficiency. The DPPH free radical scavenging assay was employed to assess the antioxidant activity of the synthesized compounds. Compound <b>4c</b> demonstrated the highest potency with an IC₅₀ value of 12.46 μg/mL. Molecular docking of compound <b>4c</b> with soybean lipoxygenase-1 (PDB ID: 3pzw) revealed significant binding energy (-7.9 kcal/mol), further supported by iMODS normal-mode analysis indicating stable binding and providing insights into its conformational flexibility during the interaction. This work underscores SBPASA's utility as a recyclable, sustainable catalyst for green transformations and a gateway to bioactive compounds with pharmaceutical relevance.