Synthesis, Biological Evaluation, and Molecular Docking Investigation of New Series of Azoimino-Sulfathiazole (AIST) Derivatives.

Sulfonamides are important compounds with special applications in pharmaceuticals due to their antibacterial and antiparasitic properties, and they are known as sulfa drugs (SDs). In this study, we focused on the multifunctional therapeutic compound sulfathiazole (ST) and investigated its hybridization of imine bonds with various azo compounds. A series of novel azoimino-sulfathiazoles (AIST) was successfully synthesized using a one-pot three-component reaction (3MCR) methodology. Additionally, we reported the design and synthesis of two ST derivatives bound to an azo group in a 3MCR dish. The structure of the newly synthesized AISD after separation and purification was examined and confirmed by TLC, M.P., FT-IR, 1H NMR, and 13C NMR. Furthermore, their cytotoxicity was evaluated via MTT assay. The antibacterial, antioxidant, and anticancer activities of the AISD compounds were assessed using the MTT assay, focusing on the PC-3 human prostate cancer cell line. The results showed good resistance to E. coli and S. aureus, with inhibition zones of 27 and 31 mm, respectively, compared to standard penicillin G. More importantly, certain AIST compounds exhibited superior antibacterial activity compared to penicillin G. To understand the mode of action of the proteins and potential interactions, docking calculations were performed using the target proteins 1FDW, 3FC2, and 5GWK. 5GWK achieved the highest placement score, followed by 1FDW and 3FC2, which showed strong closeness. A detailed analysis of the ligand–protein interactions revealed the strongest interaction with human topoisomerase II alpha (5GWK) as the target protein. [ABSTRACT FROM AUTHOR]