Synthesis, SC-XRD-characterization and biological evaluation of pyrazolone derivatives
Journal of Molecular Structure, cilt.1373, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 1373
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.molstruc.2026.146545
- Dergi Adı: Journal of Molecular Structure
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica, Compendex, INSPEC, Academic Search Ultimate (EBSCO), Engineering Source (EBSCO)
- Anahtar Kelimeler: DFT, In silicoADME/T, In vitroAntioxidant activity, Molecular docking, MTT, Pyrazolone, SC-XRD
- Karadeniz Teknik Üniversitesi Adresli: Hayır
Özet
This paper focuses on the design and synthetic preparation of novel pyrazolone-derived compounds, as well as their comprehensive structural elucidation using spectral, in vitro, and in silico techniques. The antioxidant activities of the compounds were evaluated via DPPH radical scavenging, pH-dependent DPPH, and MTT-based cellular assays. Kinetic (k/t1/2 values of 0.0964 min-1/7.19 min) and pH-dependent DPPH antioxidant assays, together with cellular viability measurements (IC₅₀ ≈130 µM), compound III emerged as the lead candidate in the series. Solid-state structures and molecular conformations of the compounds were determined by single-crystal X-ray diffraction (SC-XRD) analysis. The results showed that I and II, both containing rigid sp²-hybridized imine bridges, adopt nearly planar conformations, whereas the reduction of this bridge to a flexible sp³-hybridized amine linkage in III increases conformational flexibility, resulting in two distinct conformers linked by NH···O hydrogen bonds forming non-centrosymmetric dimers. Calculations utilizing the Density Functional Theory (DFT) approach contributed to the elucidation of their structural properties, such as reactivity and electronic properties. Their pharmacological potential was evaluated with ADME/T parameters. The molecular interactions of the compounds with key antioxidant enzymes, which are human glutathione peroxidase 1 (GPX1), catalase (CAT), and superoxide dismutase 1(SOD1), were evaluated through molecular docking simulations to elucidate their radical-scavenging mechanisms. The in vitro and in silico findings demonstrate that the synthesized pyrazolone derivatives possess significant antioxidant activity and favourable pharmacokinetic profiles, highlighting their potential as biocompatible antioxidant lead candidates.