# Design, synthesis, structural characterization, and antioxidant potential of novel triazole- and oxadiazole-based hydrazide-hydrazone derivatives: spectroscopic, DFT, and molecular docking studies

## TL;DR

Scientists created new chemical compounds with antioxidant properties and tested their effectiveness using experiments and computer modeling.

## Contribution

The study introduces novel triazole- and oxadiazole-based hydrazide-hydrazone derivatives with promising antioxidant activity and structure-activity insights.

## Key findings

- Several synthesized compounds showed antioxidant activity comparable to or better than ascorbic acid in DPPH assays.
- DFT calculations revealed optimized geometries and molecular properties that correlate with antioxidant potential.
- Molecular docking studies identified favorable interactions with the Keap1–Nrf2 complex, suggesting a mechanism for antioxidant activity.

## Abstract

A novel series of hydrazide-hydrazone derivatives incorporating 1,2,4-triazole and 1,2,4-oxadiazole scaffolds was synthesized through multistep condensation and cyclization reactions starting from 4-nitrobenzohydrazide. The structures of the synthesized compounds (MI-1 to MI-9) were confirmed by FTIR, 1H NMR, and 13C NMR spectroscopy, complemented by elemental and mass analyses. Their antioxidant potential was assessed in vitro using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, where several derivatives demonstrated comparable or superior activity to ascorbic acid. To elucidate structure–activity relationships, density functional theory (DFT) calculations were performed to analyze optimized geometries, frontier molecular orbitals (HOMO–LUMO), and molecular electrostatic potential (MEP) surfaces. Furthermore, molecular docking studies against the Keap1–Nrf2 complex revealed favorable binding interactions for select compounds, highlighting their potential as antioxidant modulators through Nrf2 pathway activation. The combined spectroscopic, theoretical, and docking insights provide a comprehensive understanding of the structure–activity relationships of these novel heterocyclic derivatives and support their potential application as antioxidant therapeutic leads.

The online version contains supplementary material available at 10.1186/s13065-025-01698-6.