Synthesis, DFT Analysis, and Evaluation of Antibacterial and Antioxidant Activities of Sulfathiazole Derivatives Combined with In Silico Molecular Docking and ADMET Predictions.

Synthetic modifications of sulfathiazole derivatives become an interesting approach to enhance their biological properties in line with their applications. As a result, sulfathiazole derivatives become a good candidate and potential class of organic compounds to play an important role towards medicinal chemistry. In present study, one thiazole derivative and two new sulfathiazole derivatives are synthesized with 94% and 72-81% yields, respectively. Furthermore, the synthesized compounds were evaluated for their in vitro antibacterial activity against two Gram-negative (E. coli and P. aeruginosa) and two Gram-positive bacterial strains (S. pyogenes and S. aureus) by disk diffusion method. Among synthesized compounds, compound 11a showed potent inhibitory activity against Gram-negative, E. coli with 11.6 ± 0.283 mm zone of inhibition compared to standard drug sulfamethoxazole (15.7 ± 0.707 mm) at 50 mg/mL. The radical scavenging activities of these compounds were evaluated using DPPH radical assay, and compound 11a showed the strongest activity with IC₅₀ values of 1.655 μg/mL. The synthesized compounds were evaluated for their in silico molecular docking analysis using S. aureus gyrase (PDB ID: 2XCT) and human myeloperoxidase (PDB ID: 1DNU) and were found to have minimum binding energy ranging from -7.8 to -10.0 kcal/mol with 2XCT and -7.5 to -9.7 with 1DNU. Compound 11a showed very good binding score -9.7 kcal/mol with both of the proteins and had promising alignment with in vitro results. Compound 11b also showed high binding scores with both proteins. Drug likeness and ADMET of synthesized compounds were predicted. The DFT analysis of synthesized compounds was performed using Gaussian 09 and visualized through Gauss view 6.0. The structural coordinates of the lead compounds were optimized using B3LYP/6-31 G (d,p) level basis set without any symmetrical constraints. Studies revealed that all the synthesized compounds might be candidates for further antibacterial and antioxidant studies.