What question did this study set out to answer?

The aim is to synthesize vanillin-pyrazole hybrids and evaluate their antioxidant properties and structural characteristics.

April 17, 2026

Synthesis, Crystal Structure, Characterization, In Vitro and In Silico Evaluation of Vanillin‐Pyrazole Heterocyclic Hybrids as Potent Antioxidants

Puntos clave

The aim is to synthesize vanillin-pyrazole hybrids and evaluate their antioxidant properties and structural characteristics.
Synthesis of hybrids via 1,3-dipolar cycloaddition reaction
Characterization using NMR spectroscopy, HRMS, and X-ray diffraction
Investigation of electronic properties using density functional theory calculations
In vitro evaluation using TAC and FRAP assays
Molecular docking and dynamics simulations with human cytochrome P450 and carbonyl reductase
Compound 4a shows the smallest HOMO-LUMO gap, indicating high electron-donating ability
Compounds 4a-c, 6a, and 6b exhibit antioxidant activity with IC50 values between 19.59 to 30.37 µM
Compounds 4a and 6b demonstrate remarkable activities of IC50 92.13 and 102.64 µM in the FRAP assay
Molecular docking results correlate well with observed antioxidant effects
All compounds exhibit favorable ADMET properties for potential drug development.

Resumen

Herein, we report the synthesis of a series of vanillin-pyrazole hybrids through a 1,3-dipolar cycloaddition reaction. The structures of these compounds were elucidated by various analytical methods, including NMR spectroscopy and HRMS, where compound 4a was further confirmed by x-ray diffraction. Their electronic properties were investigated through density function theory calculations at the B3LYP/6-311G(d,p). Moreover, the in vitro antioxidant activity of all compounds was evaluated by total antioxidant capacity and ferric reducing antioxidant power assays. As a result, compound 4a had the smallest HOMO-LUMO gap, indicating high electron-donating ability, while 4b showed the highest EHOMO (-5.688 eV), lowest hardness, and a narrow gap (∼4.20 eV). Additionally, compounds 4a-c, 6a, and 6b exhibited an important antioxidant activity with IC50 values ranging from 19.59 to 30.37 µM in the TAC method, compounds 4a and 6b showed remarkable activity of IC50 (92.13 and 102.64 µM, respectively) in the FRAP assay. Molecular docking and molecular dynamics simulations were performed to investigate the binding mode and behavior of 4a-c and 6b with human cytochrome P450 (CYP2C9) and human carbonyl reductase-1 (HCBR1), which were in good agreement with the observed antioxidant effects. These assessments revealed that vanillin-pyrazole hybrids could be used as promising derivatives in the quest for potent antioxidants. The ADMET properties indicated favorable drug-like properties for all compounds. Overall, compounds 4a, 4b, and 6b combine potent antioxidant activity with promising pharmacokinetic characteristics, highlighting vanillin-pyrazole hybrids as potential drug candidates for antioxidant therapy.

Me gusta

Guardar