Design, synthesis, and evaluation the anti-β-lactamase activity of new sulphathiazole-derived monobactam compounds
Iraqi Journal of Pharmacy,
2020, Volume 17, Issue 1, Pages 19-36
AbstractObjectives: β-Lactams are the most successful antibiotics for the management of infectious diseases. Unfortunately, the bacterial production of β-lactamase that hydrolyzes the β-lactam ring can inactivate these drugs. The use of β-lactamase inhibitors like (clavulanic acid) in combination with the β-lactams may reduce this inactivation. The prevalent β-lactamase phenotype is the TEM-1 of class A released by Gram-positive and Gram-negative bacteria.
Methods: The docking study with TEM-1 β-lactamase lead to synthesize of new 5 monobactam compounds as the acid chloride derivatives reacted with the Schiff bases compound forming the monobactam ring. The final 5 synthesized compounds were characterized using physical and spectroscopic methods and tested biologically by evaluating their MIC values against 4 strains of β-lactamase Gram-positive and Gram-negative bacteria. The results were compared with those acquired from using clavulanic acid as a co-inhibiter with amoxicillin against the tested bacteria.
Results: The results revealed that 2 synthesized compounds showed an anti β-lactamase effect resemble to that of clavulanic acid.
Conclusion: As conclusion; the β-lactamase active pocket prefers hydrophobic substituents, as the synthesized products with these groups appeared to have the highest affinity.
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