Design, Synthesis, Biological Assessment, and Computational Analysis of Sulfathiazole Schiff Bases

Sulfathiazole-based Schiff Bases (SBs) have fascinated science with their broad-spectrum pharmacological properties and potential therapeutic applications. However, their efficacy and molecular interactions require further investigation. This investigation sought to synthesize sulfathiazole-based SBs and appraise their biological properties through characterization, in vitro assays, molecular docking, density functional theory, and ADME analysis. Sulfathiazole SBs synthesized by reacting sulfathiazole with various aryl aldehydes in equimolar ratios were characterized using UV–Vis, FTIR, CHNSO, 1 H NMR, and [Formula: see text]C NMR spectroscopy and assessed for antibacterial, antifungal activities, antioxidant, in vitro antidiabetic, and anti-inflammatory potential using different assays. Molecular docking, DFT calculations, and ADMET analysis were conducted to scrutinize binding affinity, stability, and pharmacokinetic properties. The synthesized SBs exhibited notable antibacterial and antifungal activity. Compound 10b demonstrated strong antioxidant potential (IC 50 [Formula: see text] 55.93 ± 0.56[Formula: see text]g/mL), while compounds 7b, 9b, and 12b showed significant antidiabetic effects. Additionally, 7b (IC 50 [Formula: see text] 53.97 ± 0.89[Formula: see text]g/mL) and 9b (IC 50 [Formula: see text] 60.22 ± 0.81 [Formula: see text]g/mL) displayed superior anti-inflammatory activity. Computational studies confirmed their potential as drug candidates. The integration of biophysical and chemical approaches provides a detailed understanding of their electronic structure, stability, and intermolecular interactions with biological targets. These results establish a strong foundation for further preclinical investigations, advancing their potential applications in drug discovery and development.