One-Pot Synthesis of 1,2,3-Triazole-Phthalimide Derivatives as Potential Antibacterial: Molecular Docking, DFT and...

A novel series of 1,2,3-triazoles bearing a phthalimide moiety (5a-g) was designed and synthesized as promising antibacterial agents. The synthesis involved reacting N-substituted phthalimide with substituted azidobenzene via click chemistry using dimethyl sulfoxide as a solvent. The structures of the synthesized compounds were confirmed using FT-IR, ¹H NMR, ¹³C NMR, and UV-visible spectroscopy. Compound 5c showed exceptional inhibition towards two types of bacterial strains, S. aureus and E. coli with zones of inhibition of (34 and 23 mm) respectively compared to the ceftriaxone (22 and 19 mm) respectively. Molecular docking studies identified the type of interactions between our derivatives and two types of bacterial residues, leading to the strong inhibitory activity. The validity of these interactions was further achieved by using PyRx and Discovery studio, which confirmed that 5c and 5d, display considerable binding affinity, exhibiting lowest binding energies (-9.4 and - 9.5, kcal/mol) in comparison with ceftriaxone (-8.8 kcal/mol) with staphylococcus aureus (PDB ID:7O4b), and compounds 5d, 5e, and 5f display considerable binding affinity, exhibiting the lowest binding energies (-8.1, -8.6 and - 8.7, kcal/mol) in comparison with ceftriaxone (-7.4 kcal/mol) with Escherichia coli (PDB ID:7V9X). The consistency between in vitro and in silico results validated the reliable antibacterial probability of these compounds. Computational studies, including FMO analysis, the HOMO-LUMO energy gaps, were utilized to evaluate reactivity, stability, and inhibitory profiles of derivatives. In summary, the study provides a strong indication that these designed 1,2,3-triazole-bearing phthalimide moieties exert remarkable antibacterial activity, in silico ADMET studies showed favorable pharmacokinetic and drug-likeness properties, supporting the potential of the synthesized compounds as promising drug candidates. S. aureus and E. coli, justifying additional in vitro studies.