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Potent and selective inhibitors of class A β-lactamase: 7-prenyloxy coumarins
Hadi Safdari1, Alireza Neshani2, Ali Sadeghian3
1Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran.
Abstract:
Class A and D β-lactamases are the main causes of resistance against β-lactam antibiotics, especially the penam group, in Staphylococcus aureus. On the basis of the potentiator property of ethanolic extracts of Ferula szowitsiana root on penicillin, MIC values observed for resistant S. aureus, the main naturally occurring compounds in these extracts, auraptene, umbelliprenin and galbanic acid, were evaluated for β-lactamase inhibitory activity. Amongst them auraptene showed the most potent inhibitory activity (IC50=21±1.5 μM) toward class A β-lactamase, whereas no inhibition was observed for class D β-lactamase. To obtain the structure activity relationship of the mentioned compounds and rationalize the enzyme inhibitory results, docking analysis was performed for both groups of β-lactamases. Docking analysis showed that the compounds have 100-500-fold lower bonding affinity toward the class D β-lactamase than toward the class A enzyme.
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