The sulfonamide group represents a crucial functional moiety in both organic synthesis and pharmaceutical development. sulfonamides exhibit remarkable chemical stability and unique reactivity, making them valuable intermediates and end-products in a wide range of chemical transformations. Historically, sulfonamide derivatives gained prominence as the first class of synthetic antibiotics, revolutionizing antimicrobial therapy in the early 20th century. Beyond their antibacterial properties, sulfonamides have demonstrated a broad spectrum of biological activities, including antidiabetic, antitumor, and anti-inflammatory effects.On the other hand, computational chemistry plays a pivotal role in the rational design and development of novel sulfonamide-based molecules with potential biological or industrial applications. Through advanced molecular modeling, quantum chemical calculations, and molecular docking techniques. These in silico methods enable efficient screening of large libraries of sulfonamide analogs, identification of promising lead compounds, and optimization of their pharmacokinetic and pharmacodynamic profiles. Moreover, density molecular dynamics simulations offer valuable insights into the geometry, stability, and interaction mechanisms of these compounds at the atomic level.In the present study, a series of sulfonylimine derivatives were synthesized via the condensation of aromatic aldehydes with sulfanilamide, yielding the target compounds in good yields. To investigate their therapeutic potential particularly as anti-inflammatory agents, molecular docking studies were performed against phosphodiesterase 4 (PDE4), a key enzyme involved in the regulation of inflammatory responses through modulation of intracellular cyclic adenosine monophosphate (cAMP) levels. Inhibition of PDE4 results in elevated cAMP concentrations, which activate protein phosphorylation cascades that suppress the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α).