Lactoperoxidase Inhibition of Celecoxib Derivatives Containing the Pyrazole Linked-Sulfonamide Moiety: Antioxidant Capacity, Antimicrobial Activity, and Molecular Docking Studies


BAYRAK S., Gerni S., Öztürk C., Almaz Z., Bayrak Ç., Kılınç N., ...Daha Fazla

Journal of Biochemical and Molecular Toxicology, cilt.38, sa.11, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 38 Sayı: 11
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1002/jbt.70055
  • Dergi Adı: Journal of Biochemical and Molecular Toxicology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Applied Science & Technology Source, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, Environment Index, Food Science & Technology Abstracts, MEDLINE
  • Anahtar Kelimeler: antimicrobial and antioxidant activity, enzyme purification and inhibition, lactoperoxidase (LPO), molecular docking, pyrazole sulfonamide
  • Atatürk Üniversitesi Adresli: Evet

Özet

Celecoxib derivatives that contain the pyrazole-linked sulfonamide moiety were synthesized, and the in vitro inhibitory impacts of the aforesaid compounds against the lactoperoxidase (LPO) enzyme were researched. To this end, LPO was purified using the affinity chromatography technique with a yield of 12.63% (319.23-fold). The results showed that the aromatic pyrazole compound (compound 1) containing 2,3-dimethoxyphenyl functional groups was the most effective LPO inhibitor with a Ki value of 3.2 ± 0.7 nM and noncompetitive inhibition type. The second section of the study tested the previously synthesized compounds to reveal their antioxidant and antimicrobial properties. The above-mentioned compound also displayed high activity levels compared to standard antibiotics and antifungals, while all other compounds also showed antibacterial activity. In the three antioxidant methods we used, the compound with 2,5-dimethoxy phenyl groups obtained from the reaction of the aromatic pyrazole compound with propionic anhydride in the presence of NEt3 displayed the highest activity. Furthermore, molecular docking and molecular mechanics studies were conducted to complement and validate the experimental findings. The results obtained from these computational analyses are highly consistent with the experimental data.