Sulfamethoxazole-derived Schiff bases: Synthesis, characterization, biological activities, molecular docking, DFT, and ADME studies

• Published in: Journal of molecular structure 2024-09, Vol.1312, p.138640, Article 138640
• Main Authors: Wajid, Muhammad, Uzair, Muhammad, Muhammad, Gulzar, Siddique, Farhan, Bashir, Maryam, Nadeem, Sumaira, Ashraf, Adnan, Assad, Nasir, Mushtaq, Aamir, Rafay, Muhammad Zohaib, Aqdas, Amna, Ahmad, Sajjad, Alasmari, Abdullah F.
• Format: Article
• Language: English
• Subjects: Density functional theory; DPPH; FT-IR; Schiff bases; Sulfamethoxazole
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.138640

•Compound 4d showed exceptional antibacterial activity against K. pneumoniae, S. aureus, and S. agalactiae, outperforming sulfamethoxazole.•Compound 3d demonstrated superior antioxidant properties, surpassing ascorbic acid in the DPPH assay.•SBs were highly effective against α-amylase and α-glucosidase enzymes, with compound 7d showing the most potent inhibition, indicating potential for diabetes management.•Compound 5d significantly reduced inflammation in the protein denaturation assay, highlighting its therapeutic promise.•Computational docking and DFT calculations confirmed strong binding affinities and valuable electronic properties of the SBs, supporting their experimental efficacy. Herein, we reported the synthesis of sulfamethoxazole-derived Schiff bases (SBs) using aromatic aldehydes for in-vitro biological applications (antimicrobial, antioxidant, antidiabetic, and anti-inflammatory). Among thoroughly characterized (UV/visible, FT-IR, 1HNMR, and 13CNMR) SBs demonstrating better antibacterial activity than sulfamethoxazole, 4d depicted exceptional bacterial growth inhibition against K. pneumoniae, S. aureus, and S. agalactiae. The DPPH assay revealed the most potent free radical scavenging potential of 3d, even outperforming ascorbic acid. The in-vitro antidiabetic potential of SBs assessed using postprandial glucose absorption inhibitory against α-amylase and α-enzymes showed good potential, with 7d being efficient against both enzymes. The in-vitro anti-inflammatory potential using protein denaturation assay with diclofenac sodium as a positive control was insignificant, except for 5d, showing considerable potential (p-value < 0.0001). Molecular docking revealed that synthesized SBs have good binding affinities towards different receptor proteins, supporting the experimental results. The electronic properties calculated using DFT demonstrated a low energy gap (3.61 eV) for 1d, representing its high reactivity, among other SBs. [Display omitted]