Salicylaldehyde-derived Hydrazones: Synthesis, characterization, antibacterial activity, antioxidant and anti-inflammatory effects on LPS-induced RAW264.7 macrophage cells, drug-likeness properties, and molecular docking analysis


Demirbağ B., Yıldırım M., Çimentepe M., Necip A., Ünver H., Tiftik E. N.

Biochemical and Biophysical Research Communications, cilt.766, 2025 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 766
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1016/j.bbrc.2025.151872
  • Dergi Adı: Biochemical and Biophysical Research Communications
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE
  • Anahtar Kelimeler: Anti-Bacterial, Hydrazones, LPS, RAW264.7 cell line, Schiff base, TNF-α
  • Çukurova Üniversitesi Adresli: Hayır

Özet

The rising incidence of pathogenic microorganisms underscores the urgent need to develop innovative anti-inflammatory agents. This study aims to investigate the anti-inflammatory and antibacterial mechanisms of Schiff base (SB) derived from salicylaldehyde (SA) compounds in stimulated and unstimulated macrophage cell line (RAW264.7) cells. We synthesized and characterized SB derived from SA using 1H NMR and 13C NMR spectroscopy. Anti-bacterial and computational insights of compounds were carried out. A 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was conducted to evaluate the toxicity profile of compounds on both lipopolysaccharide (LPS)-stimulated and unstimulated RAW264.7 cells. Additionally, the levels of nuclear factor kappa B (NFκB), interleukin (IL-6), tumor necrosis factor alpha (TNF-α), and reactive oxygen species (ROS) in the cells were measured using a microplate reader. The compound SA-SB-1 (the half maximal inhibitory concentration (IC50: 39.58 μM) demonstrated strong inhibitory activity compared to SA-SB-2 (IC50: 55.64 μM). SA-SB-1 exhibited greater inhibitory effects on the expression of NFκB, IL-6, TNF-α, and ROS in LPS-stimulated RAW264.7 cells than SA-SB-2. SA-SB-1 and SA-SB-2 exhibited a minimum inhibitory concentration (MIC) value of 12 μg/mL against E. faecalis and 250 μg/mL against S. aureus, P. aeruginosa, and E. coli. The binding affinities of SA-SB-1 and SA-SB-2 were studied against various proteins, including those with PDB IDs: 2AZ5, 4ZS7, 2RAM, 3G7B, 6QXS, and 2UV0. The highest binding affinity of SA-SB-2 was found to be −9.329 kcal/mol for 2UV0. These findings are promising for the potential development of new anti-inflammatory drugs.