Etude des activités inhibitrice d'une métallo-bêta-lactamase et de la croissance de A.Baumannii des ligands bases de Schiff symétriques et de leurs complexes de zinc

Abstract

A total of five Schiff bases ligands H2L tetradentate N2O2 and N2S2 (H2L1 at the 2,3-diaminopyridine bridge), (H2L2 and H2L3 based at the 1,2-diaminobenzene bridge), (H2L4 at the 1,3-diaminopropyl bridge) and (H2L5 at the 1,2- diaminoethyl bridge) and their zinc complexes have been synthesized and characterized by routine physicochemical methods namely the melting temperature, solubility, molar conductance, UV-Vis spectrophotometry, IR-FT, NMR1H , NMR13C and elemental analysis. These molecules proved to be stable, soluble in organic solvents with the exception of H2L1 and its complex, non-electrolytes, of structures conforming to those proposed and chelating zinc. The structures of H2L2-H2L5 and their electronic properties were calculated in the gas phase using functional density theory (DFT) via the B3LYP/6-31G (d, p) method. Calculations show that the ligand H2L2 is the most reactive because it has the smaller energy gap. The ligands H2L2-H2L5 have been used as inhibitors against a semi-purified metallo-beta-lactamase (MBL) from Acinetobacter baumannii and have been shown to have a significant inhibitory effect (IC50 ≤ 58.96 μM), compared to the standard inhibitor, EDTA (IC50 = 3.98 mM). An overlap between their energy differences (HOMO, LUMO), their reactivities and their IC50, reveals that the more the energy gap decreases, the more the reactivity increases, the more the IC50 decreases and the more the ligand is effective. The same ligands and their zinc complexes were also tested as antibacterial agents. Tests have shown that these molecules are active on G + bacteria growth but inactive on G- bacteria including A.baumannii. The bacterial wall more developed in them, obviously limits the penetration of the molecule in the bacterial cell and consequently its bacteriostatic or bactericidal action.