title: Potent and selective inhibitors of class A β-lactamase: 7-prenyloxy coumarins.
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.
authors: Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran.
authors: Hadi
authors: H
authors: Safdari
authors: Student Research Committee, Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran.
authors: Alireza
authors: A
authors: Neshani
authors: Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors: Ali
authors: A
authors: Sadeghian
authors: Student Research Committee, Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran.
authors: Masoomeh
authors: M
authors: Ebrahimi
authors: Biotechnology Research Center, Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors: Mehrdad
authors: M
authors: Iranshahi
authors: 1] Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran [2] Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors: Hamid
authors: H
authors: Sadeghian
mesh_terms: D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005309:Ferula / Q000737:chemistry; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D013211:Staphylococcus aureus / Q000187:drug effects; D065093:beta-Lactamase Inhibitors
chemical_list: D003374:Coumarins; D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors