Synthesis and biological evaluation of pyrazolyl-pyrazolone derivatives: Antioxidant, anticancer activities, and molecular docking insights

Benoune R. A., Boulcina R., Dems M. A., Uğur E., Karci H., DÜNDAR M., ...Daha Fazla

Journal of Molecular Structure, cilt.1347, 2025 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1347
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1016/j.molstruc.2025.143344
  • Dergi Adı: Journal of Molecular Structure
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, Chimica, Compendex, INSPEC
  • Anahtar Kelimeler: Anticancer activity, Antioxidant activity, Cytotoxicity, Knoevenagel condensation, Molecular docking, Pyrazolyl-pyrazolone derivatives
  • İnönü Üniversitesi Adresli: Evet

Özet

In this study, a series of novel pyrazolyl-pyrazolone derivatives was synthesized via a Knoevenagel condensation reaction using trisodium citrate as a catalyst, highlighting an environmentally sustainable and cost-effective approach. The synthesized compounds were characterized through comprehensive analytical techniques, including NMR spectroscopy, HRMS, and melting point determination. Biological evaluations demonstrated diverse and promising activities: compound 6i exhibited exceptional antioxidant activity across DPPH, ABTS, and Ferric-phenanthroline assays, outperforming standard antioxidants like BHT and BHA. In parallel, anticancer assays against SH-SY5Y and HCT116 cell lines revealed compounds 6e, 6j, and 6k as potent cytotoxic agents, with IC50 values significantly lower than cisplatin, the reference drug. Notably, compound 6j showed remarkable selectivity towards cancer cells with reduced cytotoxicity on non-cancerous BEAS-2B cells. Molecular docking studies confirmed strong binding interactions of the active compounds with key cancer-related protein targets, shedding light on their mechanisms of action. These findings not only highlight the therapeutic potential of pyrazolyl-pyrazolone derivatives as dual antioxidant and anticancer agents but also emphasize the value of sustainable chemical processes in drug development.