One-pot synthesis, biological evaluation, DFT calculations and molecular docking study of 1,2,4,5-tetrasubstituted imidazole derivatives and their bismuth(III) complexes

The 1,2,4,5-tetrasubstituted imidazole derivatives bearing sterically hindered catecholic moiety and their Bi(III) complexes were synthesized and characterized by physicochemical methods. These bidentate ligands yielded Bi(III) complexes of the stoichiometry Bi(L)Cl₂, being coordinated in monoanionic form through the <i>O</i> and <i>N</i> donor atoms. All the studied compounds have been screened <i>in vitro</i> against Gram-positive (<i>B. subtilis</i>, <i>S. saprophyticus</i>), Gram-negative (<i>P. putida</i>, <i>P. vulgaris</i>) bacteria and yeasts (<i>S. cerevisiae</i>) as compared to some standard antimicrobials. The Bi(III) complexes have been found to be more active against the tested bacteria (MIC 0.061 ÷ 0.086 µmol/mL) than the parent tetrasubstituted imidazole ligands (0.165 ÷ 0.188 µmol/mL) and Bi(III) subcitrate (De-Nol) (&gt;0.568 µmol/mL). The effect of these Bi(III) complexes, as well as the parent ligands and Bi(III) subcitrate, on the production of <i>Proteus vulgaris</i> urease has also been investigated. The complexes have demonstrated a higher urease inhibition activity compared to the parent ligands and Bi(III) subcitrate. Molecular docking studies of the urease from the urease-producing bacteria have been performed in order to predict the possible interaction modes and binding energies of the tested compounds at the molecular level.