One-pot synthesis of novel hydrazinyl thiazoles using rust and Ficus benghalensis leaf derived Fe2O3/ZrO2 nano-catalyst: Their molecular docking, ADME, antidiabetic, and antioxidant study

• We developed a sustainable and retrievable Fe₂O₃/ZrO₂ nano-catalytical system, which derived from rust and Ficus benghalensis leaf extract and confirmed its efficacy for synthesis of novel hydrazinyl thiazole derivatives via one-pot operation. • Hydrazinyl thiazole derivatives were accessed from simple starting materials under eco-friendly and sustainable condition in excellent yield, which were fully confirmed by using 1 H NMR, 13 C NMR and HRMS analytical techniques. • Among the synthesized compounds, thiazole derivative 4c exhibiting significant anti-diabetic potential with IC 50 value 49.72 ± 0.8 µg/mL whereas 4b showing the highest antioxidant activity with IC 50 value 39.13±1.75 µg/mL in DPPH assays. • Molecular docking and ADME studies confirmed the drug-like properties of hydrazinyl thiazoles. • Further investigation into these compounds' mechanistic pathways and in vivo efficacy could pave the way for novel treatments in anti-diabetic and antioxidant therapies. A robust, magnetically retrievable Fe₂O₃/ZrO₂ nanocatalyst, synthesized from rust and Ficus benghalensis leaf extract, was developed and characterized using Fourier transform infrared (FTIR) spectroscopy and powder X-ray diffraction (XRD). This sustainable catalyst was employed to synthesize novel hydrazinyl thiazoles from aromatic aldehydes, thiosemicarbazide, and phenyl acyl tosylate, achieving good to excellent yields. The structures of all the thiazole derivatives were confirmed by ¹H NMR, ¹³C NMR, and high-resolution mass spectrometry (HRMS). The compounds were evaluated for anti-diabetic activity, with compound 4c displaying potent α-amylase inhibition (IC₅₀ = 49.72 ± 0.8 µg/mL). Antioxidant activity was assessed via the DPPH assay, where compound 4b exhibited the highest potency (IC₅₀ = 39.13 ± 1.75 µg/mL). Molecular docking and ADME (absorption, distribution, metabolism, and excretion) studies further revealed drug-like properties aligning with the in vitro results. This work demonstrates the efficacy of a biomass-derived Fe₂O₃/ZrO₂ nanocatalyst in designing a library of bioactive hydrazinyl thiazoles, highlighting its potential as a sustainable tool for developing therapeutically relevant scaffolds.