Synthesis, design and integrated in vitro/in silico assessment of novel cyano-amide derivatives

A novel and an efficient synthesis of a series of cyano-amide derivatives 3a-h was achieved via solvent-free reaction of benzylcyanide derivatives 1 with isocyanate derivatives 2 at room temperature. The produced components were structurally characterized by NMR spectroscopy multinuclear: 1 H and 13 C and elemental analysis. Density functional theory (DFT) calculations were used to examine electronic properties, including highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energies, as well as local and global reactivity descriptors using B3LYP in the gaussian program at the 6-311G level. The theoretical results suggest that the cyano-amide derivatives 3a-h keep semiconductor properties, with band gap energies ranging from 4.189 to 6.314 eV. Similarly, biological assays demonstrated that adducts 3b and 3f exhibited the most potent antioxidant and antibacterial activities, particularly effective against P. aeruginosa . Furthermore, molecular docking studies further highlighted promising antibacterial, antioxidant and anti-HMPV potential of cyano-amide derivatives 3a-h targeting S. aureus DNA gyrase with PDB ID: 2XCS, Human myeloperoxidase with PDB ID: 1DNU and HMPV with PDB ID: 5WB0.