Biocompatible synthesis, computational studies and therapeutic evaluation of a dibutyl (2,2-dicyano-1-phenylethyl) phosphonate derivatives targeting oxidative stress, microbial infection and cancer cells.

We synthesized a series of dibutyl (2,2-dicyano-1-phenylethyl) phosphonates using a solvent-free, one-pot reaction catalysed by L-carnitine hydroxide. This green method yielded products in 75-97% yield. Density functional theory analysis showed that these compounds have favourable HOMO-LUMO gaps and enhanced charge transfer, suggesting good nonlinear optical properties. Molecular docking indicated strong binding to key bacterial proteins. In vitro tests confirmed strong antioxidant activity (DPPH IC₅₀: 21.1-49.8 µg/mL; NO IC₅₀: 21.2-31.1 µg/mL) and effective antibacterial action against both Gram-positive and Gram-negative bacteria (inhibition zones: 2.0-3.8 mm). The compounds also inhibited cancer cell growth in five human cell lines (IC₅₀: 3.5-5.9 µM), with higher selectivity than doxorubicin over non-cancerous cells. ADMET analysis predicted good absorption, low toxicity and drug-likeness. Electron-withdrawing groups improved both biological and electronic properties. These phosphonates are promising candidates for new therapeutic development.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-025-04499-9.