Sulfaquinoxaline-derived Schiff bases: Synthesis, characterization, biological profiling, and computational modeling

Here, six sulfaquinoxaline Schiff bases were synthesized, and various analytical techniques such as FTIR, 1HNMR, and 13CNMR were employed for the characterization. Additionally, in-vitro biological studies were performed, including antibacterial, antifungal, antioxidant, antidiabetic, and anti-inflammatory activities. Computational tools such as molecular docking, DFT, and MD simulations were applied to explore the binding interactions, molecular structure, and chemical reactivity of sulfaquinoxaline SBs. Lastly, in-silico ADMET studies were performed to investigate drug-likeness properties, toxicity, and metabolism of the synthesized SBs. The prepared SBs demonstrated strong antibacterial activity against S. agalactiae and E. coli better than the standard drug, sulfaquinoxaline. The SBs possessed non-significant antioxidant (DPPH assay) and antidiabetic activities (?-amylase and ?-glucosidase). All the derivatives depicted moderate anti-inflammatory activity except 6e (IC50 131.95 µg/mL) which presented comparable activity to the standard drug, diclofenac sodium (IC50 127.27 µg/mL). Computational analyses supported the experimental results, especially for compounds 5e and 6e confirming the robust binding affinities and enduring interactions of SBs with the protein target. In-silico drug-likeness analysis and ADMET prediction demonstrated that SBs were drug-like and had a satisfactory ADMET profile. © 2024 Elsevier B.V.