Eco-friendly Synthesis, antibacterial evaluation and in-silico profiling of Thioamide derivatives as dual-action potential dual-action agents

An efficient, solvent-free synthesis of novel phosphono fluoro thioamidate derivatives 1–5 was achieved by reacting isothiocyanate derivatives with bis(2,2,2-trifluoroethyl) phosphonate at room temperature. The thioamide derivatives of 1–5 was confirmed by NMR spectroscopy ( 1 H, 13 C, 19 F and 31 P) and elemental analysis. Density Functional Theory (DFT) calculations (B3LYP/6-311G level, Gaussian) enabled structural exploration and geometry optimization, revealing optimized conformations for these derivatives. Significantly, compounds 1, 4, and 5 exhibited semiconductor properties with band gap energies ranging from 3.09 to 5.357 eV, as determined by HOMO-LUMO analysis and local/global reactivity descriptors. In addition, biological evaluation identified derivative 2 as the most potent antibacterial agent, displaying significant activity against P. aeruginosa, while the components 1 and 3 showed moderate activity against S. aureus and E. faecium . However, to corroborate these findings, molecular docking studies were conducted against S. aureus DNA gyrase (PDB: 2XCT ) and hepatitis virus proteins, including HAV with PDB ID: 1HAV , HBV (PDB IDs: 5GMZ , 5WRE and 3OX8 ) and HCV with PDB ID: 2XI3 . These simulations highlighted the antibacterial and antiviral potential of derivatives 1–5 , aligning with experimental results.