DOCKING, SYNTHESIS AND β-LACTAMASE INHIBITORY ACTIVITY EVALUATION FOR NEW AMIDE COMPOUNDS

Abstract

The beta-lactams are recognized as effective antibiotics for treating infections, yet bacterial production of β-lactamase, which hydrolyzes the beta-lactam ring, can render these drugs inactive. Combining these antibiotics with a β-lactamase inhibitor, such as clavulanic acid, mitigates this resistance. In a docking study involving Temoniera-1 (TEM-1), 1pzp, we induced the synthesis of eight amide compounds by reacting acid chloride derivatives with sulphathiazol or oxadiazol amine, forming an amide bond. The newly synthesized compounds were differentiated using physical and spectroscopic methods and verified biologically by estimating their minimum inhibitory concentration (MIC) against four strains of βlactamase G(+)ve and G(-)ve bacteria. Their anti β-lactamase behaviors were then compared with that of clavulanic acid as a co-inhibitor with amoxicillin against the same four strains of bacteria. The results indicate that four of the new amides exhibit excellent anti-β-lactamase activity and contain one or more hydrophobic residues in their structures. Halogen atoms enhance the selectivity of tower β-lactamases. Derivatives of both oxadiazole and sulfathiazole scaffolds show promising anti-β-lactamase activity as nonβ-lactam inhibitors.