Design, synthesis and anti-β-lactamase activity for new monobactam compounds

Abstract

Abstract β-Lactams are the most effective antibiotics for the treatment of infectious diseases. Unfortunately, the bacterial β-lactamase breaks down the β-lactam ring, and hence deactivates these drugs. The use of β-lactamase inhibitors (e.g., clavulanic acid) in combination with β-lactams reduces this resistance. The prevalent β-lactamase is the Temoniera (TEM-1) of class A from Gram-positive and Gram-negative bacteria. Hence, this research involves design, docks (computer calculation), synthesizes series of monobactam compounds, then studying their biological and β-lactamase inhibitor activities. The docking study lead to synthesize a new 9 monobactam compounds, these compounds were synthesized from the reaction of selected acid chlorides with the synthesized Schiff bases. The structures of the synthesized compounds were characterized on the basis of the physical and spectral data. The monobactam compounds were tested biologically via evaluation of their Minimum Inhibitory Concentration (MIC) against 4 strains of β-lactamase Gram-positive and Gram-negative bacteria. The gained results of their anti β-lactamase activities were compared with that of clavulanic acid as a co-inhibiter with amoxicillin against the same 4 strains of bacteria. The biological study results revealed that three of the synthesized compounds showed an anti β-lactamase effect resemble to that of clavulanic acid. It has been concluded that the β-lactamase active pocket prefers hydrophobic substituents, as the synthesized products with these groups appear with the highest affinity.