Ag2WO4 nanocatalyst-driven green synthesis of pyrano[2,3-d]pyrimidinones: an integrated experimental, DFT, and cytotoxic investigation

Abstract

The development of environmentally sustainable routes for synthesizing bioactive heterocycles remains a central objective in contemporary medicinal chemistry. In this work, silver tungstate (Ag₂WO₄) nanoparticles were synthesized and characterized by X-ray diffraction and scanning electron microscopy, confirming their crystalline structure and surface morphology. The prepared nanoparticles served as an efficient heterogeneous nanocatalyst for the one-pot green synthesis of pyrano[2,3-d]pyrimidinone derivatives (2a–2h) in an ethanol–water medium, affording excellent yields under mild conditions and demonstrating high catalytic efficiency with strong alignment to green chemistry principles. Comprehensive in silico analyses, including density functional theory (DFT), molecular docking, molecular dynamics (MD) simulations, and ADME screening, were performed to elucidate the electronic distribution, binding interactions, and pharmacokinetic profiles of the synthesized scaffolds. Docking studies revealed that compounds 2g (−7.58 kcal mol⁻¹) and 2h (−7.34 kcal mol⁻¹) exhibited binding affinities comparable to the reference drug afatinib (−8.01 kcal mol⁻¹). In vitro cytotoxic evaluation against A549 lung carcinoma cells further identified compound 2h as the most potent derivative (IC₅₀ = 39.29 µM), significantly outperforming the unsubstituted analogue 2a (IC₅₀ = 120.65 µM). Overall, this integrated experimental, computational, and biological study establishes Ag₂WO₄ as a robust and sustainable nanocatalyst, offering an efficient pathway for the rapid synthesis of pyrano[2,3-d]pyrimidinone scaffolds with promising anticancer potential.